Compositions for use in the treatment of chlamydia.

Abstract

This invention relates to compositions (e.g., vaccine compositions) which can be used to immunise against Chlamydia infections. The compositions comprise Chlamydia sp. antigens and antigen combinations which can be used to immunise against Chlamydia sp., used in the form of nucleic acids (e.g., mRNAs) encoding antigenic proteins or in the form of recombinant protein antigens.

Description

COMPOSITIONS FOR USE IN THE TREATMENT OF CHLAMYDIA FIELD OF THE INVENTION

[001] The present invention relates to the field of treatment and prevention of Chlamydia infections. In particular, the invention relates to antigens and combinations of antigens that can be used as vaccines to immunize against Chlamydia sp. infection. The vaccines can be administered as nucleic acids (e.g., mRNAs) encoding antigenic proteins or as recombinant protein antigens. BACKGROUND

[002] Chlamydias are intracellular bacterial pathogens responsible for a variety of infections, including human sexually transmitted diseases and eye infections (Trachoma) caused by Chlamydia trachomatis. The genus Chlamydia also includes the species Chlamydia abortus, Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia pecorum, Chlamydia felis, and Chlamydia cavias.

[003] Chlamydia trachomatis (C. trachomatis) comprises three biovars that lead to a range of pathological conditions in humans and are further subdivided into serovars.1 The AC serovars (A, B, Ba, and C), of the trachoma biovar, can cause chlamydial conjunctivitis or trachoma, a disease that can result in blindness.2 The DK serovars (D, E, F, G, H, I, J, and K), of the genital tract biovar, cause disease in the genital tract.3 The lymphogranuloma venereum biovar, serovars L1-3 (L1, L2, and L3), causes invasive urogenital and anorectal infections and has become particularly associated with men who have sex with men infected with HIV.4

[004] C. trachomatis (serovars DK) is the most common bacterial agent of sexually transmitted infections. 5In 2020, the WHO estimated 129 million new C. trachomatis infections. These are Petition 870250077861, dated 01 / 09 / 2025, p. 11 / 418 2 / 306 of public health concern, particularly because untreated infections are often asymptomatic or have minimal symptoms, but contribute to the transmission of the pathogen. Furthermore, if left untreated, the infection can, among other things, lead to salpingitis, endometritis, pelvic inflammatory disease (PID), ectopic pregnancy, tubal factor infertility, and may increase the risk of HIV transmission or acquisition and the development of cervical carcinoma.6 Although C. trachomatis infections can be effectively controlled through antibiotic therapy, due to the high prevalence of cases and the often late diagnosis of asymptomatic cases, C. trachomatis has become a leading cause of female infertility worldwide.7 There is a need to develop an effective vaccine against C. trachomatis as a sustainable strategy to contain C. trachomatis infection rates. DESCRIPTION OF THE INVENTION

[005] Chlamydia sp. antigens and antigen combinations that can be used to immunize against Chlamydia sp. have been provided.

[006] In particular, antigens derived from a native polypeptide of the Chlamydia trachomatis outer membrane major protein (MOMP) and C. trachomatis antigens other than MOMP elicited robust T cell responses, particularly induction of IFN-γ-producing CD4+ T cells and / or B cell responses (i.e., antibodies) when administered by mRNAs encoding the relevant antigens. In particular, T cell responses are considered critical for protective immunity.

[007] Consequently, the invention provides polypeptides Modified MOMPs, chimeric VD polypeptides of MOMPs and CT443, CT584, CT600 and CT812 polypeptides of Chlamydia sp. and nucleic acids comprising a nucleotide sequence that encodes Petition 870250077861, dated 01 / 09 / 2025, page 12 / 418 3 / 306 ca tais polipeptides.

[008] The polypeptide antigens described in this document can be administered by, i.e., in the form of a nucleic acid (e.g., mRNA) comprising a nucleotide sequence encoding said polypeptide. MOMP

[009] MOMP is an integral membrane porin protein8 found in Chlamydia sp. bacteria. It constitutes about 60% of the protein mass in the Chlamydia trachomatis membrane9 and contains multiple B and T cell epitopes10. In C. trachomatis infection, MOMP is an immunodominant antigen. Chlamydia sp. native MOMP polypeptides include five conserved domains separated by four surface-exposed variable domains (VD1, VD2, VD3, and VD4).11,12. Thus, in a Chlamydia sp. native MOMP polypeptide, VD1, VD2, VD3, and VD4 are surface-exposed loops. Within Chlamydia species (e.g., C. trachomatis), native MOMP polypeptides vary in their VD sequences across different serovars.13,14 Within each C. trachomatis serovar, native MOMP polypeptide sequences are highly conserved with over 98% sequence identity. In C. serovars...In trachomatis, protein sequences are highly conserved, with the exception of surface-exposed VDS. Neutralizing antibody epitopes have been mapped to VDS.15,16,17,18,19.

[0010] It has been recognized that IFN-γ-producing CD4+ T cells are essential for protective immunity; in fact, cellular production of IFN-γ has been shown to be strongly correlated with protection20 and CD4+ T cells appear to be essential, since HIV+ women have a higher risk of chlamydia reinfection21. There is also evidence that antibodies against C. trachomatis (i.e., B cell-mediated responses) alone may not prevent reinfection. Petition 870250077861, dated 01 / 09 / 2025, page 13 / 418 4 / 306 infection and the presence of anti-C. trachomatis IgG may even increase the risk of incident infection.22 Anti-C. trachomatis antibodies have demonstrated accelerated clearance of a primary C. trachomatis challenge in the presence of CD4+ T cells in mice; however, in the absence of CD4+ T cells, the primary challenge was not eliminated.23

[0011] A native Chlamydia sp. MOMP polypeptide, as used herein, comprises a mature form of a full-length native Chlamydia sp. MOMP polypeptide without its native signal peptide sequence and a full-length native Chlamydia sp. MOMP polypeptide including its native signal peptide sequence. Preferably, the Chlamydia sp. referred to herein is Chlamydia trachomatis. A native C. trachomatis MOMP polypeptide may be from one of the AC, DK, or L1-L3 serovars, for example, DK serovars. In some embodiments, the native C. trachomatis MOMP polypeptide is from one of the DG serovars. In some preferred embodiments, the native C. trachomatis MOMP polypeptide is from serovar E. Exemplary sequences of Chlamydia sp. MOMP polypeptides. Natives comprising the native signal peptide sequence are provided by SEQ IDs 1-4.

[0012] The amino acid sequence of a MOMP polypeptide of C. trachomatis causes infection and causes damage to SEQ ID NO: 2: MKKLLKSVLV FAALSSASSL QALPVGNPAE PSLMIDGILW EGFGGDPCDP CTTWCDAISM RMGYYGDFVF DRVLKTDVNK EFQMGDKPTS TTGNATAPTT LTARENPAYG RHMQDAEMFT NAACMALNIW DRFDVFCTLG ASSGYLKGNS ASFNLVGLFG DNENQSTVKT NSVPNMSLDQ SVVELYTDTA FSWSVGARAA LWECGCATLG ASFQYAQSKP Petition: 870250077861, on September 1, 2025, p. 14 / 418 5 / 306 KVEELNVLCN AAEFTINKPK GYVGQEFPLA LIAGTDAATG TKDASIDYHE WQASLALSYR LNMFTPYIGV KWSRASFDAD TIRIAQPKSA TAIFDTTTLN PTIAGAGDVK ASAEGQLGDT MQIVSLQLNK MKSRKSCGIA VGTTIVDADK YAVTVETRLI DERAAHVNAQ FRF (SEQ ID NO: 2)

[0013] The native signal peptide sequence corresponds to residues 1-22 in the MOMP amino acid sequence of C. trachomatis serovar E (SEQ ID NO: 2) and is shown underlined. Residues 23393 of SEQ ID NO: 2 correspond to the mature full-length native MOMP polypeptide form of C. trachomatis serovar E that does not have the native signal peptide sequence. The VD1-VD4 sequences of the C. trachomatis serovar E MOMP polypeptide are shown in bold and underlined text above.

[0014] The native MOMP polypeptide of Chlamydia sp. may comprise the following sequence: (i) a MOMP polypeptide native to serovar D of C. trachomatis (SEQ ID NO: 1) or its mature form (residues 23-393 of SEQ ID NO: 1); (ii) a MOMP polypeptide native to the F serovar of C. trachomatis, (SEQ ID NO: 3) or its mature form (residues 23-395 of SEQ ID NO: 3); or (iii) a native MOMP polypeptide from C. trachomatis serovar G (SEQ ID NO: 4) or its mature form (residues 23-395 of SEQ ID NO: 4).

[0015] The native MOMP polypeptide of Chlamydia sp. comprises five conserved domains separated by four variable surface-exposed domains (VD1, VD2, VD3, and VD4). For example, in the native MOMP polypeptide of C. trachomatis serovar E, VD1 (SEQ ID NO: 9) corresponds to amino acid residues 86-105 of SEQ ID NO: 2, Petition 870250077861, dated 01 / 09 / 2025, page 15 / 418 6 / 306 VD2 (SEQ ID NO: 10) corresponds to amino acid residues 161-181 of SEQ ID NO: 2, VD3 (SEQ ID NO: 11) corresponds to amino acid residues 245-260 of SEQ ID NO: 2, and VD4 (SEQ ID NO: 12) corresponds to amino acid residues 309-337 of SEQ ID NO: 2. The conserved domains correspond to amino acid residues 23-85 (first conserved domain); 106-160 (second conserved domain); 182-244 (third conserved domain), 261-308 (fourth conserved domain) and 338-393 (fifth conserved domain). For serovar E, VD4 (SEQ ID NO: 12) corresponds to positions 309-337 in SEQ ID NO: 2 and the fifth conserved domain corresponds to positions 338-393 in SEQ ID NO: 2 or VD4 (SEQ ID NO: 883) corresponds to positions 309-338 in SEQ ID NO: 2 and the fifth conserved domain corresponds to positions 339-393 in SEQ ID NO: 2.

[0016] For serovars D, F, and G of C. trachomatis, the residues corresponding to VD1, VD2, VD3, and VD4 and the five conserved domains are shown in Table 1. For serovar D, VD4 (SEQ ID NO: 8) corresponds to positions 309-337 in SEQ ID NO: 1 and the fifth conserved domain corresponds to positions 338-393 in SEQ ID NO: 1 or VD4 (SEQ ID NO: 882) corresponds to positions 309-338 in SEQ ID NO: 1 and the fifth conserved domain corresponds to positions 339-393 in SEQ ID NO: 1. For serovar F, VD4 (SEQ ID NO: 16) corresponds to positions 310-339 in SEQ ID NO: 3 and the fifth conserved domain corresponds to positions 340-395 in SEQ ID NO: 3 or VD4 (SEQ ID NO: 884) corresponds to positions 310-340 in SEQ ID NO: 3, and the fifth preserved domain corresponds to positions 341-395 in SEQ ID NO: 3.For serovar G, VD4 (SEQ ID NO: 20) corresponds to positions 310-339 in SEQ ID NO: 4 and the conserved fifth domain corresponds to positions 340-395 in SEQ ID NO: 4 or VD4 (SEQ ID NO: 885) corresponds to positions 310-340 in SEQ ID NO: 4 and the conserved fifth domain corresponds to position 340-395 in SEQ ID NO: 4. Petition 870250077861, dated 01 / 09 / 2025, p. 16 / 418 7 / 306 ções 341-395 em SEQ ID NO: 4. Table 1 - VD1-VD4 and the first, second, third, fourth, and fifth conserved domains in a native MOMP polypeptide from C. trachomatis serovars, DG. Serovar Domain Positions in SEQ ID NO: SEQ ID NOs D First conserved domain 23-85 in SEQ ID NO: 1 VD1 86-105 in SEQ ID NO: 1 5 Second conserved domain 106-160 in SEQ ID NO: 1 VD2 161-181 in SEQ ID NO: 1 6 Third conserved domain 182-244 in SEQ ID NO: 1 VD3 245-260 in SEQ ID NO: 1 7 Fourth conserved domain 261-308 in SEQ ID NO: 1 Any VD4 309-337 in SEQ ID NO: 1 8 Fifth conserved domain 338-393 in SEQ ID NO: 1 Or VD4 309-338 in SEQ ID NO: 1 882 Fifth conserved domain 339-393 in SEQ ID NO: 1 E First preserved domain 23-85 in SEQ ID NO: 2 VD1 86-105 in SEQ ID NO: 2 9 Second preserved domain 106-160 in SEQ ID NO: 2 VD2 161-181 in SEQ ID NO: 2 10 Third preserved domain 182-244 in SEQ ID NO: 2 Petition 870250077861, dated 01 / 09 / 2025, page 17 / 418 8 / 306 VD3 245-260 in SEQ ID NO: 2 11 Fourth preserved domain 261-308 in SEQ ID NO: 2 Any VD4 309-337 in SEQ ID NO: 2 12 Fifth preserved domain 338-393 in SEQ ID NO: 2 Or VD4 309-338 in SEQ ID NO: 2 883 Fifth preserved domain 339-393 in SEQ ID NO: 2 F First preserved domain 23-85 in SEQ ID NO: 3 VD1 86-106 in SEQ ID NO: 3 13 Second preserved domain 107-161 in SEQ ID NO: 3 VD2 162-182 in SEQ ID NO: 3 14 Third preserved domain 183-245 in SEQ ID NO: 3 VD3 246-261 in SEQ ID NO: 3 15 Fourth preserved domain 262-309 in SEQ ID NO: 3 Any VD4 310-339 in SEQ ID NO: 3 16 Fifth preserved domain 340-395 in SEQ ID NO: 3 Or VD4 310-340 in SEQ ID NO: 3 884 Fifth preserved domain 341-395 in SEQ ID NO: 3 G First preserved domain 23-85 in SEQ ID NO: 4 VD1 86-106 in SEQ ID NO: 4 17 Petition 870250077861, dated 01 / 09 / 2025, page 18 / 418 9 / 306 Second preserved domain 107-161 in SEQ ID NO: 4 VD2 162-182 in SEQ ID NO: 4 18 Third preserved domain 183-245 in SEQ ID NO: 4 VD3 246-261 in SEQ ID NO: 4 19 Fourth preserved domain 262-309 in SEQ ID NO: 4 Any one VD4 310-339 in SEQ ID NO: 4 20 Fifth preserved domain 340-395 in SEQ ID NO: 4 Or VD4 310-340 in SEQ ID NO: 4 885 Fifth preserved domain 341-395 in SEQ ID NO: 4

[0017] Native MOMP polypeptides of C. trachomatis from serovars AC, HK or L1-L3, or other native MOMP polypeptides of C. trachomatis comprise VD1-VD4 and conserved domains at positions corresponding to the residue numbering established for native MOMP polypeptides of DG serovars of C. trachomatis, for example, serovar E.

[0018] The sequences of other C. native MOMP polypeptides. The MOMP polypeptides of C. trachomatis, including those from serovars AC, HK, or L1-L3, are well-known and available in public databases. For example, amino acid sequences of native C. trachomatis MOMP polypeptides are available in the Uniprot (https: / / www.uniprot.org / ) and NCBI (https: / / www.ncbi.nlm.nih.gov / ) databases. Nucleic acid sequences encoding native C. trachomatis MOMP polypeptides can be obtained from the NCBI database. Petition 870250077861, dated 01 / 09 / 2025, p. 19 / 418 10 / 306 (https: / / www.ncbi.nlm.nih.gov / ). The positions of VDS and conserved domains within other native C. trachomatis MOMP polypeptides are well known and, in any case, can be determined by aligning sequences of, for example, C. trachomatis serovars D, E, F, and G with sequences of other native C. trachomatis MOMP polypeptides and searching for regions of high sequence conservation to identify, for example, conserved domains. Modified MOMP polypeptides

[0019] Modified MOMP polypeptides comprising non-native loop sequences instead of native VD sequences of Chlamydia sp. MOMPs have been generated. The inventors recognized that such modified MOMP polypeptides can be used to elicit a protective immune response against Chlamydia sp. infection. In particular, the inventors demonstrated that such modified MOMP polypeptides induce a T cell response, including CD4+ T cells, such as IFN-γ-producing CD4+ T cells. Notably, IFN-γ-producing CD4+ T cells are believed to be important in protection against Chlamydia sp. infections. Elimination of native VD sequences can therefore reduce B cell-mediated responses (e.g., antibodies) (e.g., to B cell epitopes in VDs), while prioritizing T cell responses to MOMPs, e.g., to sequences in conserved domains that are conserved across serovars.The inventors showed that modified MOMP polypeptides can elicit a cross-serovar T-cell immune response, that is, a T-cell immune response that is cross-reactive against two or more serovars of Chlamydia sp., for example, the DG and J serovars of C. trachomatis.

[0020] It has therefore been demonstrated that these modified MOMP polypeptides are suitable vaccine candidates that can be used. Petition 870250077861, dated 01 / 09 / 2025, page 20 / 418 11 / 306 of these as independent antigens or in combination with other Chlamydia sp. antigens that can elicit B cell-mediated responses (e.g., antibodies) and / or T cell-mediated responses in an individual, such as one or more chimeric VD polypeptides of MOMP provided herein and / or one or more CT443, CT584, CT600, or CT812 polypeptides of Chlamydia sp. provided herein, in order to promote long-lasting memory T cell responses and protective immunity against infection. A modified MOMP polypeptide, as described herein, may be delivered by a nucleic acid comprising a nucleotide sequence encoding the modified MOMP polypeptide.

[0021] Consequently, in one aspect, the invention provides a nucleic acid comprising a nucleotide sequence encoding a modified MOMP polypeptide, wherein the modified MOMP polypeptide has an amino acid sequence comprising two or more conserved domain sequences of a native Chlamydia sp. MOMP polypeptide and a non-native loop sequence between the conserved domain sequences. In a further aspect, the invention provides a modified MOMP polypeptide having an amino acid sequence comprising two or more conserved domain sequences of a native Chlamydia sp. MOMP polypeptide and a non-native loop sequence between the conserved domain sequences.

[0022] In a preferred embodiment, the modified MOMP polypeptide does not comprise a variable Chlamydia sp. MOMP domain between the two or more conserved domain sequences. Thus, in a modified MOMP polypeptide, a non-native loop sequence can replace a VD sequence of the native Chlamydia sp. MOMP polypeptide. A modified MOMP polypeptide can, therefore Petition 870250077861, dated 01 / 09 / 2025, page 21 / 418 12 / 306 therefore, omit a native Chlamydia sp. MOMP VD sequence between the two or more conserved domain sequences and include a non-native loop sequence between the two or more conserved domain sequences.

[0023] Replacement of native VD MOMP sequences of Chlamydia sp. by non-native loops removes B cell epitopes (e.g., antibody epitopes) found in native Chlamydia sp. MOMP VDs. Removal of these B cell epitopes can reduce B cell-mediated responses to antigen in an individual (e.g., to B cell epitopes in native MOMP VDs). This can advantageously increase T cell responses to MOMP in an individual, for example, to sequences in conserved MOMP domains that share a high degree of identity between MOMP serovars. The modified MOMP polypeptides of the invention can therefore elicit a cross-serovar T cell immune response in an individual, i.e., a T cell immune response that is cross-reactive against two or more Chlamydia sp. serovars (e.g., cross-reactive against two or more serovars (e.g., serovars DG and J) of C. trachomatis).Thus, the modified MOMP polypeptides of the invention may be able to enhance T cell-mediated responses (e.g., relative to a corresponding native MOMP polypeptide). The modified MOMP polypeptides of the invention may be able to enhance a CD4+ T cell-mediated response (e.g., a CD4+ IFNγ+ T cell response, such as the CD4+ IFNγ+ IL2+ TNFα+ T cell response), for example, relative to a corresponding native MOMP polypeptide. The modified MOMP polypeptides of the invention may be able to induce a T cell response (e.g., an antigen-specific T cell response) in an individual. The T cell response may be immunodominant. Thus, the modified MOMP polypeptide... Petition 870250077861, dated 01 / 09 / 2025, page 22 / 418 13 / 306 of the invention may be able to induce a population of T cells responsive to a native Chlamydia sp. MOMP polypeptide in an individual. In some embodiments, the T cell response is a CD4+ T cell response (e.g., CD4+ IFNγ+ T cell response). In some embodiments, the T cell response is an IFNγ+ IL2+ TNFα+ CD4+ T cell response.

[0024] Non-native loop sequences refer to sequences that are not native to any Chlamydia sp. MOMP VD (VD1, VD2, VD3, or VD4) of any serovar. In some embodiments, the non-native loop sequences are no more than 40%, no more than 35%, no more than 30%, no more than 25%, no more than 20%, no more than 15%, no more than 10%, or no more than 5% identical to any native Chlamydia sp. MOMP VD (VD1, VD2, VD3, or VD4) sequences of any serovar. In some forms, the non-native loop sequences are no more than 40%, no more than 35%, no more than 30%, no more than 25%, no more than 20%, no more than 15%, no more than 10%, or no more than 5% identical to the MOMP VD sequences (VD1, VD2, VD3, or VD4) of C. trachomatis serovar E (SEQ ID Nos: 9-12).

[0025] Non-native loop sequences can allow conserved domain sequences in the modified MOMP polypeptide to form a beta-barrel structure, for example, to maintain a beta-barrel structure of the conserved domains of a native Chlamydia sp. MOMP polypeptide. Thus, in the modified MOMP polypeptides of the invention, the two or more conserved domain sequences are linked by a non-native loop sequence so that the conserved domain sequences form a beta-barrel structure (e.g., composed of antiparallel beta strands). The beta-barrel structure can be as predicted in silico (e.g., using Petition 870250077861, dated 01 / 09 / 2025, page 23 / 418 14 / 306 Alphafold2 (Deepmind) software).

[0026] In silico modeling can be used to create a 3D structure of a native MOMP protein, comprising a beta barrel with VD1-VD4 sequences as loops linking individual beta strands. The VD1-VD4 loops are located on the same side of the barrel structure (exposed surface in a native MOMP polypeptide). Non-native loop sequences can be mapped onto VD loops in an in silico model, and suitable non-native loop sequences can be determined by a person skilled in the art. Suitable non-native loop sequences include peptide sequences that can span the distance between the ends of conserved domains flanking a native VD, for example, as modeled in silico. The distance can correspond to the distance in, for example, angstroms, as determined by the 3D in silico model between the last conserved domain residue before the VD sequence to the first conserved domain residue after the VD sequence.

[0027] Non-native loop sequences can exclude sequence motifs that are found in an individual's proteome (e.g., human), for example, sequence motifs of 8 or more, 9 or more, 10 or more, 11 or more, 12 or more, 13 or more, 14 or more, or 15 or more amino acids in length. Sequence motifs excluded from the individual's proteome (e.g., human proteome) are typically 8 or more amino acids in length. This helps minimize unwanted cross-reactivity due to homology between the antigen and self proteins.

[0028] A non-native loop sequence may be between 3 and 30 amino acids long, for example, between 4 and 20 amino acids long. In some embodiments, a non-native loop sequence that replaces VD1 may have a sequence according to SEQ ID NO: 462 or 466 (for example, SEQ ID NO: 462). In some Petition 870250077861, dated 01 / 09 / 2025, p. 24 / 418 In 15 / 306 embodiments, a non-native loop sequence replacing VD2 may have a sequence corresponding to SEQ ID NO: 463 or 467 (e.g., SEQ ID NO: 463). In some embodiments, a non-native loop sequence replacing VD3 may have a sequence corresponding to SEQ ID NOs 464 or 468 (e.g., SEQ ID NO: 464). In some embodiments, a non-native loop sequence replacing VD4 may have a sequence corresponding to SEQ ID NO: 465 or 469 (e.g., SEQ ID NO: 465). Typically, a modified MOMP polypeptide may comprise four non-native loop sequences corresponding to SEQ ID NOs 462-465 in place of VD1, VD2, VD3, and VD4, respectively. A modified MOMP polypeptide may alternatively comprise four non-native loop sequences according to SEQ IDs 466-469 in place of VD1, VD2, VD3, and VD4, respectively.

[0029] A conserved domain sequence of a native Chlamydia sp. MOMP polypeptide refers to a conserved domain sequence of a MOMP polypeptide from a Chlamydia species of any serovar or a variant thereof. Variants include sequences with at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity (preferably at least 95% identity) with a conserved domain of a Chlamydia sp. MOMP polypeptide of any serovar.In some embodiments, the conserved domain sequences of the modified MOMP polypeptide are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical (at least 95% identical) to a conserved domain of. Petition 870250077861, dated 01 / 09 / 2025, page 25 / 418 16 / 306 a native MOMP polypeptide of a Chlamydia sp. of any serovar (e.g., a conserved domain as defined in Table 1). Variants also include truncated forms of native conserved domains of a Chlamydia sp. MOMP polypeptide, for example, where a conserved domain sequence in a modified MOMP polypeptide lacks up to 3, 5, 8, 10, 15, 20, 25, or 30 (e.g., up to 3 or 5, e.g., up to 3) amino acids from a conserved MOMP domain sequence of a native Chlamydia species. In some embodiments, the conserved domain sequences of the modified MOMP polypeptide lack up to 3 or 5 amino acids from a conserved MOMP domain sequence of a native Chlamydia species. The conserved domain boundaries for C. trachomatis serovars D, E, F, and G are presented in Table 1.

[0030] In some embodiments, the modified MOMP polypeptide comprises two, three, four, or five conserved domains of a native Chlamydia sp. MOMP polypeptide or variants thereof. In some embodiments, a modified MOMP polypeptide comprises five conserved domain sequences of a native Chlamydia sp. MOMP polypeptide or variants thereof. In some embodiments, the modified MOMP polypeptide comprises all five conserved full-length domains of a native Chlamydia sp. MOMP polypeptide. The conserved domains of the modified MOMP polypeptide may collectively have at least 95% sequence identity with the conserved domains of a native MOMP polypeptide (e.g., serovar E MOMP).In some embodiments, the conserved domain sequences of the modified MOMP polypeptide collectively have at least 90% or at least 95% sequence identity (e.g., at least 95%) with the conserved domains of a polypeptide. Petition 870250077861, dated 01 / 09 / 2025, page 26 / 418 17 / 306 native MOMP deo (e.g., conserved domains as defined in Table 1).

[0031] The conserved domains of a modified MOMP polypeptide may comprise conserved MOMP domain sequences from a C. trachomatis serovar (e.g., DK serovars, as well as DG serovars). In some embodiments, conserved domains of a modified MOMP polypeptide may comprise conserved MOMP domain sequences from the E serovar of C. trachomatis.

[0032] A modified MOMP polypeptide may comprise a non-native loop sequence between each of the conserved domain sequences. Thus, a modified MOMP polypeptide may comprise one, two, three, or four non-native loop sequences. One or more non-native loop sequences may replace one, two, three, or four of the corresponding native VD loops. Native VDs may be retained between any remaining conserved domains. The modified MOMP polypeptide may have five conserved domain sequences from a native Chlamydia sp. MOMP polypeptide. In some embodiments, the modified MOMP polypeptide does not comprise any native Chlamydia sp. MOMP VDs between any of the conserved domain sequences. In some embodiments, the modified MOMP polypeptide comprises four non-native loop sequences and does not comprise any native Chlamydia sp. MOMP VDs between the conserved domain sequences.In some embodiments, the modified MOMP polypeptide does not comprise any native Chlamydia sp. MOMP VDs (or fragments of at least 5, 6, or 7 consecutive amino acids thereof).

[0033] In some embodiments, the modified MOMP polypeptide comprises (1) all five conserved domain sequences Petition 870250077861, dated 01 / 09 / 2025, page 27 / 418 18 / 306 of a Chlamydia sp. MOMP polypeptide from C. trachomatis of any serovar and (2) four non-native loop sequences, wherein a non-native loop sequence is located between each of the conserved domain sequences and, wherein, the modified MOMP polypeptide does not comprise any native Chlamydia sp. MOMP variable domain between any of the conserved domain sequences, further wherein the non-native loop sequences are between 3 and 30 amino acids in length and not more than 40% identical to any native Chlamydia sp. MOMP VD (VD1, VD2, VD3 or VD4) sequence of any serovar.

[0034] A modified MOMP polypeptide may comprise an amino acid sequence (e.g., from the N-terminal to the C-terminal) according to the formula: C1 - L1 - C2 (Formula I), where C1 and C2 are two conserved domain sequences of a native Chlamydia sp. MOMP polypeptide and L1 is a non-native loop sequence.

[0035] In some embodiments, the modified MOMP polypeptide comprises an amino acid sequence (e.g., from the N-terminal to the C-terminal) according to the formula: C1 - L1 - C2 - L2 - C3 (Formula II), where C1, C2, and C3 are three conserved domain sequences of a native Chlamydia sp. MOMP polypeptide, and L1 and L2 are non-native loop sequences.

[0036] In some embodiments, a modified MOMP polypeptide comprises an amino acid sequence (e.g., from the N-terminal to the C-terminal) according to the formula: C1 - L1 - C2 - L2 - C3 - L3 - C4 (Formula III), where C1, C2, C3, and C4 are four conserved domain sequences of a native Chlamydia sp. MOMP polypeptide, and L1, L2, and L3 Petition 870250077861, dated 01 / 09 / 2025, p. 28 / 418 19 / 306 are non-native loop sequences.

[0037] In some embodiments, a modified MOMP polypeptide comprises an amino acid sequence (e.g., from the N-terminal to the C-terminal) according to the formula: C1 - L1 - C2 - L2 - C3 - L3 - C4 - L4 - C5 (Formula IV) where C1, C2, C3, C4 and C5 are five conserved domain sequences of a native Chlamydia sp. MOMP polypeptide and L1, L2, L3 and L4 are non-native loop sequences.

[0038] Conserved domain sequences and non-native loop sequences may be as described in this document.

[0039] In some embodiments, C1-C5 corresponds to the first, second, third, fourth, and fifth conserved domains of a native Chlamydia sp. MOMP polypeptide, respectively (e.g., as defined in Table 1).

[0040] Consequently, in some embodiments, a nucleic acid of the invention comprises a nucleotide sequence encoding a modified MOMP polypeptide comprising or consisting of the sequence shown in Formula I, II, III or IV, preferably IV.

[0041] In some embodiments, the modified MOMP polypeptide comprises a sequence conforming to any of the SEQ ID NO: 486-489 (e.g., SEQ ID NO: 486) or a sequence that has at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity therewith. In some embodiments, a modified MOMP polypeptide comprises a sequence with at least 90% identity to SEQ ID NO 486-489 (e.g., SEQ ID NO: Petition 870250077861, dated 01 / 09 / 2025, p. 29 / 418 20 / 306 486). In some embodiments, a modified MOMP polypeptide comprises a sequence with at least 95% identity to SEQ ID NO 486-489 (e.g., SEQ ID NO: 486).

[0042] In some embodiments, the nucleic acid comprising a nucleotide sequence encoding a modified MOMP polypeptide comprises a nucleotide sequence conforming to any of the SEQ ID NO: 551-566 (e.g., SEQ ID NO: 551) or a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98 % or at least 99% (for example, at least 75%) of identity with the same.Typically, nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 551 or a sequence that has at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% (e.g., at least 75%) identity with the same. In some embodiments, the nucleic acid comprises a nucleotide sequence that encodes a secretory signal peptide sequence as described herein, for example, a secretory signal peptide sequence according to SEQ ID NO: 187.

[0043] In one embodiment, the nucleic acid of the invention is an mRNA comprising or consisting of (for example, consisting of) the Petition 870250077861, dated 01 / 09 / 2025, p. 30 / 418 21 / 306 following structural elements: (1) a cap 5'; (2) an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; (3) a protein coding region having the nucleic acid sequence according to SEQ ID NO: 213 optionally followed by a stop codon (e.g., TGA); (4) an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO:839 and (5) a poly(A) tail.

[0044] In one embodiment, the nucleic acid of the invention is an mRNA comprising or consisting of (for example, consisting of) the following structural elements: (1) a chapter 5' with the following structure: THE (2) an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; (3) a protein-coding region having the nucleic acid sequence according to SEQ ID NO:213; (4) an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO:839 and (5) a poly(A) tail.

[0045] In some embodiments, the 3' end of (1) is directly linked to the 5' end of (2) via a 3' to 5' phosphodiester bond; the 3' end of (2) is directly linked to the 5' end of (3) via a 3' to 5' phosphodiester bond; the Petition 870250077861, dated 01 / 09 / 2025, p. 31 / 418 22 / 306 The 3' end of (3) is directly linked to the 5' end of (4) via a 3' to 5' phosphodiester bond; and the 3' end of (4) is directly linked to the 5' end of (5) via a 3' to 5' phosphodiester bond. In some embodiments, the mRNA is chemically modified, and the chemical modification comprises N1-methylpseudouridine in place of each uridine. The mRNA can be encapsulated in an LNP. VD chimeric polypeptides of MOMP

[0046] Immunization with chimeric VD polypeptides from Chlamydia sp. MOMPs comprising VD sequences from different C. trachomatis serovars has been shown to elicit potent antibody responses. In particular, the inventors showed that mRNAs encoding chimeric VD polypeptides from MOMPs that combined VD sequences from serovars exhibiting lower levels of VD sequence identity with each other compared to other serovars successfully induced potent antibody (IgG) responses. Chimeric VD polypeptides from MOMPs containing VD domains, of which only one is from a particular serovar, were able to elicit robust IgG responses against that serovar.The IgG antibody response levels obtained using mRNAs encoding chimeric VD polypeptides of MOMP were higher than those induced by immunization with an mRNA encoding a polypeptide combining four VD4 sequences from serovars D, E, F, and G (which was based on the polypeptide described in Anja W. Olsen, et al., Protection Against Chlamydia trachomatis Infection and Upper Genital Tract Pathological Changes by Vaccine-Promoted Neutralizing Antibodies Directed to the VD4 of the Major Outer Membrane Protein, The Journal of Infectious Diseases, Volume 212, Issue 6, 2015, Pages 978-989). Furthermore, the IgG antibody response levels obtained using mRNAs encoding chimeric VD polypeptides of MOMP... Petition 870250077861, dated 01 / 09 / 2025, page 32 / 418 23 / 306 were higher than those induced by immunization with an mRNA encoding a native MOMP protein. The inventors also demonstrated that immunization with chimeric VD polypeptides of Chlamydia sp. MOMP of the invention elicited a potent antibody response (e.g., IgG) against C. trachomatis elementary bodies (EBS). The induced antibodies were cross-reactive against EBS from different C. trachomatis serovars. The inventors also demonstrated that a VD polypeptide of Chlamydia sp. MOMP of the invention induced a T-cell response, including CD4+ and CD8+ T cells, as well as IFNγ-producing CD4+ and CD8+ T cells. The inventors demonstrated that the chimeric VD polypeptides of the invention are suitable vaccine candidates.

[0047] Thus, in another aspect, the invention provides a nucleic acid comprising a nucleotide sequence encoding a chimeric variable domain (VD) polypeptide of Chlamydia sp. MOMP, wherein the chimeric VD polypeptide of MOMP comprises an amino acid sequence comprising two or more VD sequences of Chlamydia sp. MOMP from different serovars of Chlamydia sp. In a further aspect, the invention provides a chimeric VD polypeptide of Chlamydia sp. MOMP, wherein the chimeric VD polypeptide of MOMP comprises an amino acid sequence comprising two or more VD sequences of Chlamydia sp. MOMP from different serovars of Chlamydia sp. The native VD sequences of MOMP are highly variable among Chlamydia sp. serovars and comprise epitopes that induce a B-cell immune response (i.e., antibodies).A chimeric VD polypeptide of MOMP of the present invention can elicit a B cell response (i.e., antibody response), for example, an antigen-specific antibody response, in an individual. The anti-response... Petition 870250077861, dated 01 / 09 / 2025, p. 33 / 418 24 / 306 body may be an IgG response. Induced antibodies may bind to C. trachomatis elementary bodies. The terms chimeric VD construct of MOMP, chimeric VD polypeptide of Chlamydia sp., and chimeric VD polypeptide of MOMP are used interchangeably in this document.

[0048] Thus, a chimeric VD polypeptide of the invention comprising two or more VD sequences of different Chlamydia sp. serovars can elicit a B cell response (i.e., antibody) against more than one C. trachomatis serovar, for example, a cross-serovar response. Thus, the chimeric VD polypeptide of the present invention can elicit a B cell response (antibody) against two or more Chlamydia sp. serovars. The response can be a protective antibody response.

[0049] MOMP VD sequences of C. trachomatis were compared and different levels of sequence variation were found among serovars. The MOMP VD sequences of some serovars were identical or had a high level of sequence identity (e.g., at least 70%), while for other serovars there was a greater degree of sequence variation. For example, the VD1 sequences of serovars D and E have a high level of sequence identity, and the VD1 sequences of serovars F and G are identical. However, there is a much higher level of variation between the VD1 sequences of (i) serovar D or E and (ii) serovar F or G. The VD2 sequences of serovars D and E have a high level of sequence identity, and similarly the VD2 sequences of serovars F and G have a high level of sequence identity. However, there is a much greater level of variation between the VD2 sequences of (i) serovar D or E and (ii) serovar F or G.The VD3 sequences of serovars D and F are identical, and the VD3 sequences of serovars F and G have a high level of sequence identity. The VD3 sequence of serovar E has one. Petition 870250077861, dated 01 / 09 / 2025, p. 34 / 418 25 / 306 lower percentage of sequence identity compared to the VD3 sequences of serovars D / F than compared to serovar G. However, the inventors discovered that the VD3 sequence of serovar E contains amino acid motifs that are homologous to sequences found in the human proteome. For VD4, serovars D and E sequences have a high level of sequence identity, and similarly, serovars F and G sequences have a high level of sequence identity. However, there is a much higher level of sequence variation between the VD4 sequences of (i) serovar D or E and (ii) serovar F or G.

[0050] A chimeric VD polypeptide of MOMP of the invention may therefore comprise two VD1 sequences of MOMP from different serovars of a Chlamydia sp., wherein the two VD1 sequences have less sequence identity with each other than with VD1 sequences of other serovars of Chlamydia sp. In some embodiments, the two VD1 sequences of MOMP from different serovars of a Chlamydia sp. in the chimeric VD polypeptide of MOMP are no more than 70%, 69%, 68%, 67%, 66%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25% identical (e.g., no more than 50% identical) to each other. Serovars can be selected from among the DK serovars of C. trachomatis, for example, D, E, F, and G.

[0051] A chimeric VD polypeptide of MOMP of the invention may comprise two VD2 sequences of MOMP from different serovars of Chlamydia sp., wherein the two VD2 sequences have less sequence identity with each other than with VD2 sequences of other serovars of Chlamydia sp. In some embodiments, the two VD2 sequences of MOMP from different serovars of Chlamydia sp. in the chimeric VD polypeptide of MOMP are no more than 80%, 79%, 78%, 77%, 76%, 75%, 55%, 50%, 60%, 70%, 65%, 45%, 40%, 35%, 30%, 25% identical (e.g., no more than Petition 870250077861, dated 01 / 09 / 2025, p. 35 / 418 26 / 306 rather than 50%) among themselves. Serovars can be selected from among the DK serovars of C. trachomatis, for example, D, E, F, and G.

[0052] A chimeric VD polypeptide of MOMP of the invention may comprise two VD3 sequences of MOMP from different serovars of Chlamydia sp., wherein the two VD3 sequences have a lower sequence identity to each other than to VD3 sequences of other serovars of Chlamydia sp. In some embodiments, the two VD3 sequences of MOMP from different serovars of Chlamydia sp. In the chimeric VD polypeptide of MOMP, no more than 87%, 86%, 85%, 84%, 83%, 82%, 55%, 50%, 60%, 70%, 65%, 75%, 81%, 80%, 45%, 40%, 35%, 30%, and 25% are identical (e.g., no more than 70%) to each other. In other embodiments, the chimeric MOMP comprises a single VD3 domain of MOMP. Serovars may be selected from among the DK serovars of C. trachomatis, for example, D, E, F, and G.

[0053] A chimeric VD polypeptide of MOMP of the invention may comprise two VD4 sequences of MOMP from different serovars of Chlamydia sp., wherein the two VD4 sequences have less sequence identity with each other than with VD4 sequences of other serovars of Chlamydia sp. In some embodiments, the two VD4 sequences of MOMP from different serovars of Chlamydia sp. in a chimeric VD polypeptide of MOMP may be no more than 77%, 76%, 75%, 74%, 73%, 72%, 60%, 55%, 50%, 71%, 70%, 65%, 45%, 40%, 35%, 30%, 25% identical (e.g., no more than 60% identical) to each other. Serovars can be selected from among the DK serovars of C. trachomatis, for example, D, E, F, and G.

[0054] In preferred modes, VD sequences of MOMP in the chimeric polypeptide VD of MOMP exclude sequence motifs that are found in an individual's proteome (by Petition 870250077861, dated 01 / 09 / 2025, p. 36 / 418 27 / 306 example, human), for example, sequence motifs of 8 or more, 9 or more, 10 or more, 11 or more, 12 or more, 13 or more, 14 or more, or 15 or more (e.g., 8 or more) amino acids in length. Sequence motifs excluded from the individual's proteome (e.g., human proteome) typically have 8 or more amino acids in length. As explained above, this helps minimize unwanted cross-reactivity.

[0055] In preferred embodiments, the chimeric VD polypeptide of MOMP comprises conserved domain sequence portions of a native Chlamydia sp. MOMP polypeptide flanking each of the two or more VD sequences of MOMP.

[0056] The chimeric polypeptide VD of MOMP may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 MOMP VD sequences. In some embodiments, the chimeric MOMP VD polypeptide comprises seven MOMP VD sequences.

[0057] Chlamydia sp. may be C. trachomatis and the serovars may be DK.

[0058] The chimeric polypeptide VD of MOMP may comprise MOMP VDs of two, three, four, five, six, seven, or eight different serovars, for example, DK serovars of C. trachomatis. In some embodiments, the chimeric MOMP VD polypeptide comprises MOMP VDs of four different serovars, for example, DG serovars of C. trachomatis.

[0059] The chimeric polypeptide VD of MOMP may comprise (i) two VD1 sequences of MOMP from different serovars of Chlamydia sp.; and / or (ii) two VD2 sequences of MOMP from different serovars of Chlamydia sp.; and / or (iii) one VD3 sequence of MOMP and / or (iv) two VD4 sequences of MOMP from different serovars of Chlamydia sp. In other embodiments, there are two VD3 sequences of MOMP from different serovars of Chlamydia sp. The different so Petition 870250077861, dated 01 / 09 / 2025, page 37 / 418 28 / 306 rovars can be selected from serovars D, E, F, or G of C. trachomatis.

[0060] A chimeric VD MOMP polypeptide of the invention may therefore comprise a VD MOMP sequence from C. trachomatis serovar D or E and a VD MOMP sequence from C. trachomatis serovar F or G. In some embodiments, the chimeric VD MOMP polypeptide comprises a VD1 MOMP sequence from C. trachomatis serovar D or E and a VD1 MOMP sequence from C. trachomatis serovar F or G (for example, a VD1 MOMP sequence from C. trachomatis serovar E and a VD1 MOMP sequence from C. trachomatis serovar G). In some embodiments, the chimeric VD polypeptide of MOMP comprises a VD2 sequence of MOMP from serovar D or E of C. trachomatis and a VD2 sequence of MOMP from serovar F or G of C. trachomatis (for example, a VD2 sequence of MOMP from serovar D of C. trachomatis and a VD2 sequence of MOMP from serovar G of C. trachomatis). In some embodiments, the chimeric VD polypeptide of MOMP comprises a VD3 sequence of MOMP from serovar D, F, or G of C.trachomatis (e.g., serovar F). In some embodiments, the chimeric MOMP VD polypeptide comprises a MOMP VD4 sequence from C. trachomatis serovar D or E and a MOMP VD4 sequence from C. trachomatis serovar F or G (e.g., a MOMP VD4 sequence from C. trachomatis serovar D and a MOMP VD4 sequence from C. trachomatis serovar F).

[0061] A chimeric VD MOMP polypeptide of the invention may comprise two, three, or four VD MOMP sequences from C. trachomatis serovars D or E and two, three, or four VD MOMP sequences from C. trachomatis serovars F or G. In some embodiments, the chimeric VD MOMP polypeptide comprises one VD MOMP sequence from C. trachomatis serovar D or E and one sequence from serovar F or G. Petition 870250077861, dated 01 / 09 / 2025, p. 38 / 418 29 / 306 MOMP VD sequence of C. trachomatis serovar F or G for each of MOMP VD1, VD2, VD3 and VD4. In preferred embodiments, the chimeric MOMP VD polypeptide comprises only one MOMP VD3 sequence, which corresponds to the VD3 of C. trachomatis serovar D, F or G (e.g., serovar F).

[0062] A chimeric VD polypeptide of MOMP may comprise at least one (for example, one, two, three or four) of (i)-(iv): (i) a MOMP VD1 sequence from serovar D and a MOMP VD1 sequence from serovar F or a MOMP VD1 sequence from serovar E and a MOMP VD1 sequence from serovar F; and / or (ii) a MOMP VD2 sequence from serovar E and a MOMP VD2 sequence from serovar F or a MOMP VD2 sequence from serovar D and a MOMP VD2 sequence from serovar G and / or (iii) a MOMP VD3 sequence from serovar G or a MOMP VD3 sequence from serovar F and / or (iv) a MOMP VD4 sequence from serovar E and a MOMP VD4 sequence from serovar G or a MOMP VD4 sequence from serovar D and a MOMP VD4 sequence from serovar F, wherein serovars D, E, F or G are from C. trachomatis. In some embodiments, the MOMP VD chimeric polypeptide comprises four of (i)-(iv).In some embodiments, the chimeric MOMP VD polypeptide comprises (i) a MOMP VD1 sequence from serovar E and a MOMP VD1 sequence from serovar G and (ii) a MOMP VD2 sequence from serovar D and a MOMP VD2 sequence from serovar G and (iii) a MOMP VD3 sequence from serovar F and (iv) a MOMP VD4 sequence from serovar D and a MOMP VD4 sequence from serovar F, wherein serovars D, E, F, or G are of C. trachomatis. The MOMP VD1 sequence from serovar F of C. trachomatis is the same as the MOMP VD1 sequence from serovar G of C. trachomatis.

[0063] In some embodiments, the chimeric polypeptide VD of Petition 870250077861, dated 01 / 09 / 2025, p. 39 / 418 30 / 306 MOMP comprises: (i) a VD1 sequence of MOMP from serovar D and a VD1 sequence of MOMP from serovar F, a VD2 sequence of MOMP from serovar E and a VD2 sequence of MOMP from serovar F, a VD3 sequence of MOMP from serovar G, a VD4 sequence of MOMP from serovar E and a VD4 sequence of MOMP from serovar G; or (ii) a VD1 sequence of MOMP from serovar E and a VD1 sequence of MOMP from serovar F, a VD2 sequence of MOMP from serovar D and a VD2 sequence of MOMP from serovar G, a VD3 sequence of MOMP from serovar F, a VD4 sequence of MOMP from serovar D and a VD4 sequence of MOMP from serovar F, wherein serovars D, E, F, or G are from C. trachomatis. In some embodiments, the chimeric polypeptide VD of MOMP comprises VD sequences of MOMP as in (i). Typically, the chimeric VD polypeptide of MOMP comprises VD sequences of MOMP as in (ii).

[0064] Typically, the chimeric VD polypeptide of MOMP comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to an N-glycosylation site in a native Chlamydia sp. MOMP polypeptide, for example, in one or more VD domains of MOMP.

[0065] A chimeric VD polypeptide of MOMP, as described in this document, may comprise conserved domain sequence portions that are conserved domain sequence portions of a Chlamydia sp. native MOMP polypeptide flanking the VD in its Chlamydia sp. native MOMP polypeptide. The conserved domain sequences flanking the VD in its Chlamydia sp. native MOMP polypeptide may be immediately adjacent to the VD sequence.

[0066] Each conserved domain sequence portion in a MOMP chimeric VD polypeptide may comprise between 3 and 30 amino acid residues (e.g., between 4 and 20) of a sequence Petition 870250077861, dated 01 / 09 / 2025, p. 40 / 418 31 / 306 cia of a conserved domain of a native Chlamydia sp. MOMP polypeptide, in which the 3 to 30 (e.g., 4 to 20) amino acid residues are immediately adjacent to the VD sequence in its native Chlamydia sp. MOMP polypeptide.

[0067] A chimeric VD polypeptide of MOMP, as described in this document, may comprise an amino acid sequence according to the following formula: (Ax - VDx - Bx)y - (Aw - VDw - Bw)z, where VDx comprises a VD sequence of VD1, VD2, VD3, or VD4 of a MOMP polypeptide native to serovar y of C. trachomatis; Ax comprises between 3 and 30 (e.g., between 4 and 20) amino acid residues that immediately precede VDx in a MOMP polypeptide sequence native to the y serovar of Chlamydia sp.; Bx comprises between 3 and 30 (e.g., between 4 and 20) amino acid residues that immediately follow VDx in a MOMP polypeptide sequence native to serovar y of Chlamydia sp.; VDw comprises a VD sequence of VD1, VD2, VD3, or VD4 of a MOMP polypeptide native to the z serovar of C. trachomatis; The Aw group comprises between 3 and 30 (e.g., between 4 and 20) amino acid residues that immediately precede the VDw group in a native MOMP polypeptide sequence of the Chlamydia sp. serovar z; Bw comprises between 3 and 30 (e.g., between 4 and 20) amino acid residues that immediately follow VDw in a native MOMP polypeptide sequence of the Chlamydia sp. serovar z; xew are independently selected from 1 to 4 and indicate the MOMP VD selected from VD1, VD2, VD3, or VD4. eyez are serovars of C. trachomatis (e.g., selected from serovars D, E, F, or G).

[0068] In some embodiments, the chimeric polypeptide VD of MOMP comprises a sequence in accordance with any of the Petition 870250077861, dated 01 / 09 / 2025, p. 41 / 418 32 / 306 SEQ ID NO: 490-505 (e.g., SEQ ID NO: 495 or 503 (e.g., SEQ ID NO: 503)) or a sequence that has at least 70%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with it. In some embodiments, the MOMP chimeric VD polypeptide comprises a sequence with at least 90% identity to SEQ ID NO 490-505 (e.g., SEQ ID NO: 495) or 503 (e.g., SEQ ID NO: 503). In some embodiments, the MOMP chimeric VD polypeptide comprises a sequence with at least 95% identity to either of the SEQ ID NO 490-505 (e.g., SEQ ID NO: 495) or 503 (e.g., SEQ ID NO: 503).

[0069] In some embodiments, a nucleic acid comprising a nucleotide sequence encoding a MOMP VD chimeric polypeptide comprises a nucleotide sequence according to any of the SEQ ID NO: 567-630 (e.g., SEQ ID NO: 617) or a sequence that has at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity therewith. In some embodiments, a nucleic acid comprising a nucleotide sequence encoding the chimeric polypeptide VD of MOMP comprises a nucleotide sequence that is at least 85% identical to any of the SEQ ID NO: 567-630 (e.g., Petition 870250077861, dated 01 / 09 / 2025, p. 42 / 418 33 / 306 SEQ ID NO: 617). In some embodiments, the nucleic acid comprises a nucleotide sequence that encodes a secretion signal peptide sequence as described herein, for example, a secretion signal peptide sequence according to SEQ ID NO: 187. For example, the nucleic acid may comprise a sequence according to SEQ ID NO: 870.

[0070] In one embodiment, the nucleic acid is an mRNA that comprises or consists of (e.g., consists of) the following structural elements: (1) a cap 5'; (2) an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; (3) a protein coding region having the nucleic acid sequence according to SEQ ID NO: 870 optionally followed by a stop codon (e.g., TGA); (4) an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO:839 and (5) a poly(A) tail.

[0071] In one embodiment, the nucleic acid is an mRNA that comprises or consists of (e.g., consists of) the following structural elements: (1) a chapter 5' with the following structure: THE (2) an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; (3) a protein-coding region having the sequence of acids Petition 870250077861, dated 01 / 09 / 2025, page 43 / 418 34 / 306 nucleic acids according to SEQ ID NO:870; (4) an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO:839 and (5) a poly(A) tail.

[0072] In some embodiments, the 3' end of (1) is directly linked to the 5' end of (2) via a 3' to 5' phosphodiester bond; the 3' end of (2) is directly linked to the 5' end of (3) via a 3' to 5' phosphodiester bond; the 3' end of (3) is directly linked to the 5' end of (4) via a 3' to 5' phosphodiester bond; and the 3' end of (4) is directly linked to the 5' end of (5) via a 3' to 5' phosphodiester bond. In some embodiments, the mRNA is chemically modified, and the chemical modification comprises N1-methylpseudouridine in place of each uridine. The mRNA may be encapsulated in an LNP.

[0073] In alternative embodiments, a chimeric polypeptide MOMP VD comprises three MOMP VD4 sequences selected from (i) a MOMP VD4 sequence from C. trachomatis serovar D; (ii) a MOMP VD4 sequence from C. trachomatis serovar E; (iii) a MOMP VD4 sequence from C. trachomatis serovar F; or (iv) a MOMP VD4 sequence from C. trachomatis serovar G. In some embodiments, the chimeric VD polypeptide of MOMP comprises all four VD4 (i)-(iv) domains. In some embodiments, the chimeric VD polypeptide of MOMP comprises a sequence according to any of the SEQ ID NOs: 506, 841, 842 or 843 or a sequence with at least 90% or at least 95% identity therewith. Chlamydia sp. antigens different from MOMP

[0074] Chlamydia sp. antigens other than MOMP (non-MOMP antigens) have been identified that can be used in the presentation Petition 870250077861, dated 01 / 09 / 2025, page 44 / 418 35 / 306 of the invention. Non-MOMP antigens or the nucleic acids encoding them can be supplied or used in combination with MOMP antigens, including the MOMP antigens (and the nucleic acids encoding them) described herein. These non-MOMP antigens include the Chlamydia sp. polypeptides CT443, CT584, CT600, and CT812. These antigens are highly abundant outer membrane proteins and are highly conserved across Chlamydia sp., for example, across C. trachomatis serovars. The use of any one or more of these antigens can therefore provide a cross-serovar immune response, i.e., an immune response that is cross-reactive against two or more Chlamydia sp. serovars (e.g., cross-reaction against two or more C. trachomatis serovars). The inventors have demonstrated that the C. trachomatis polypeptides CT443, CT584, CT600, and CT812...trachomatis induced a T-cell response when administered as mRNAs expressing the relevant antigen or in the form of recombinant proteins. The inventors also showed that at least mRNAs encoding the CT443, CT584, or CT600 polypeptides of C. trachomatis, as well as recombinant CT443, CT584, or CT600 proteins, induced robust antigen-specific antibody responses. CT443

[0075] It has been demonstrated that both mRNA encoding the C. trachomatis CT443 polypeptide and a recombinant C. trachomatis CT443 protein elicited IFNγ-producing T cells. Furthermore, the C. trachomatis CT443 polypeptide induced a robust IgG response when administered as an mRNA expressing the antigen or in the form of a recombinant protein. The C. trachomatis CT443 polypeptide administered as an mRNA has been shown to elicit a potent antibody response (e.g., Petition 870250077861, dated 01 / 09 / 2025, page 45 / 418 36 / 306 IgG) against C. trachomatis elementary bodies (EBS). The induced antibodies were cross-reactive against EBS from different C. trachomatis serovars. The inventors demonstrated that the C. trachomatis CT443 polypeptides of the invention are suitable vaccine candidates.

[0076] In one aspect, the invention provides a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT443 polypeptide. In another aspect, the invention provides a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT443 polypeptide. A Chlamydia sp. CT443 polypeptide for use in the present invention can elicit an antibody response (e.g., IgG) (e.g., an antigen-specific antibody response) in an individual. Induced antibodies can bind to C. trachomatis elementary bodies. The Chlamydia sp. CT443 polypeptide of the invention can elicit an antibody (IgG) response against more than one C. trachomatis serovar, for example, a cross-response between serovars. Thus, the Chlamydia sp. CT443 polypeptide of the present invention can elicit a B cell (antibody) response against two or more Chlamydia sp. serovars. The response may be a protective antibody response.

[0077] A CT443 polypeptide from Chlamydia sp. for use in the present invention can elicit a T cell response (e.g., antigen-specific T cell response) in an individual. In some embodiments, a CT443 polypeptide from Chlamydia sp. for use in the present invention induces IFN-γ-producing T cells, such as IFNγ-producing CD4+ T cells and / or IFNγ-producing CD8+ T cells in an individual.

[0078] CT443 (also called outer membrane protein B (omcB or OMPB)) is an abundant membrane protein. Petition 870250077861, dated 01 / 09 / 2025, page 46 / 418 37 / 306 external. It has been suggested that CT443 is an adhesin that promotes the interaction between the elementary body of C. trachomatis and the host cell.24 CT443, and in particular its C-terminus, has been shown to be immunogenic during human infection.25,26 It has also been reported as a protective antigen in mouse models.27,28

[0079] A Chlamydia sp. CT443 polypeptide includes a mature form of a full-length native Chlamydia sp. CT443 polypeptide without its native signal peptide sequence and immunogenic variants thereof. An immunogenic variant of a native Chlamydia sp. CT443 polypeptide is capable of eliciting an immune response (e.g., an antigen-specific immune response) in an individual, for example, a T-cell response and / or an antibody response. Immunogenic variants of a native Chlamydia sp. CT443 polypeptide include immunogenic fragments of a native Chlamydia sp. CT443 polypeptide. Immunogenic CT443 fragments include fragments of a native Chlamydia sp. CT443 polypeptide.that have at least 50, at least 75, at least 100, at least 125, at least 150, at least 175, at least 200, at least 225, at least 250, at least 275, at least 300, at least 325, at least 350, at least 375, at least 400, at least 425, at least 450, at least 475, or at least 500 amino acids in length. Typically, the CT443 polypeptide of the invention is a full-length Chlamydia sp. CT443 polypeptide. In some forms, immunogenic variants exclude sequence motifs that are found in an individual's (e.g., human) proteome, for example, sequence motifs of 8 or more, 9 or more, 10 or more, 11 or more, 12 or more, 13 or more, 14 or more, or 15 or more (e.g., 8 or more) amino acids in length. The excluded sequence motifs from the individual's proteome typically have 8 or more amino acids in length. Petition 870250077861, dated 01 / 09 / 2025, page 47 / 418 38 / 306 length. As explained above, this helps to minimize unwanted cross-reactivity.

[0080] Exemplary CT443 polypeptide sequences of Chlamydia sp. include a CT443 polypeptide sequence from Chlamydia trachomatis (see SEQ ID NO: 507 which does not have a native signal peptide sequence of the CT443 polypeptide from Chlamydia trachomatis).

[0081] In some embodiments, the CT443 polypeptide of Chlamydia sp. comprises the sequence of any of the SEQ ID NO: 507-508 (e.g., SEQ ID NO: 507) or a sequence with at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity therewith. In some embodiments, the Chlamydia sp. polypeptide CT443. It comprises a sequence with at least 90% identity to any of the SEQ IDs 507-508 (e.g., SEQ ID NO: 507). In some embodiments, the Chlamydia sp. CT443 polypeptide comprises a sequence with at least 95% identity to any of the SEQ IDs 507-508 (e.g., SEQ ID NO: 507).

[0082] In some embodiments, a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT443 polypeptide comprises a nucleotide sequence according to any of the SEQ ID NO: 707-710 (e.g., SEQ ID NO: 707) or a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least Petition 870250077861, dated 01 / 09 / 2025, page 48 / 418 39 / 306%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the same. In some embodiments, the nucleic acid comprises a nucleotide sequence that is at least 85% identical to any of the SEQ ID NO: 707-710 (e.g., SEQ ID NO: 707). In some embodiments, the nucleic acid comprises a nucleotide sequence that encodes a secretion signal peptide sequence as described in this document, for example, a secretion signal peptide sequence according to SEQ ID NO: 187. For example, the nucleic acid may comprise a sequence according to SEQ ID NO: 369.

[0083] In one embodiment, the nucleic acid is an mRNA that comprises or consists of (e.g., consists of) the following structural elements: (1) a chapter 5': (2) an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; (3) a protein coding region having the nucleic acid sequence according to SEQ ID NO: 369 optionally followed by a stop codon (e.g., TGA); (4) an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO:839 and (5) a poly(A) tail.

[0084] In one embodiment, the nucleic acid is an mRNA that comprises or consists of (e.g., consists of) the following structural elements: (1) a chapter 5' with the following structure: Petition 870250077861, dated 01 / 09 / 2025, page 49 / 418 40 / 306 O (2) an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; (3) a protein-coding region having the nucleic acid sequence according to SEQ ID NO:369; (4) an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO:839 and (5) a poly(A) tail.

[0085] In some embodiments, the 3' end of (1) is directly linked to the 5' end of (2) via a 3' to 5' phosphodiester bond; the 3' end of (2) is directly linked to the 5' end of (3) via a 3' to 5' phosphodiester bond; the 3' end of (3) is directly linked to the 5' end of (4) via a 3' to 5' phosphodiester bond; and the 3' end of (4) is directly linked to the 5' end of (5) via a 3' to 5' phosphodiester bond. In some embodiments, the mRNA is chemically modified, and the chemical modification comprises N1-methylpseudouridine in place of each uridine. The mRNA may be encapsulated in an LNP. CT584

[0086] It has been demonstrated that mRNAs encoding the C. trachomatis CT584 polypeptide and a recombinant C. trachomatis CT584 protein stimulated IFNγ-producing T cells. Furthermore, the C. trachomatis CT584 polypeptide has been shown to induce a robust IgG response when administered as an mRNA expressing the antigen or in the form of a recombinant protein. The poly Petition 870250077861, dated 01 / 09 / 2025, page 50 / 418 41 / 306 C. trachomatis CT584 peptide administered as an mRNA has been shown to elicit a potent antibody response (e.g., IgG) against C. trachomatis elementary bodies (EBS). The induced antibodies were cross-reactive against EBS from different C. trachomatis serovars. The inventors have demonstrated that the C. trachomatis CT584 polypeptides of the invention are suitable vaccine candidates.

[0087] In one aspect, the invention provides a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT584 polypeptide. In another aspect, the invention provides a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT584 polypeptide. A Chlamydia sp. CT584 polypeptide for use in the present invention can elicit an antibody response (e.g., IgG) (e.g., an antigen-specific antibody response) in an individual. The induced antibodies can bind to C. trachomatis elementary bodies. The Chlamydia sp. CT584 polypeptide of the invention can elicit an antibody (IgG) response against more than one C. trachomatis serovar, for example, a cross-response between serovars. Thus, the Chlamydia sp. CT584 polypeptide of the present invention can elicit a B cell (antibody) response against two or more Chlamydia sp. serovars. The response may be a protective antibody response.

[0088] A CT584 polypeptide from Chlamydia sp. for use in the present invention can elicit a T cell response (e.g., antigen-specific T cell response) in an individual. In some embodiments, a CT584 polypeptide from Chlamydia sp. for use in the invention induces IFNγ-producing T cells, such as IFNγ-producing CD4+ T cells and / or IFNγ-producing CD8+ T cells in an individual. Petition 870250077861, dated 01 / 09 / 2025, page 51 / 418 42 / 306

[0089] CT584 is a putative tip protein in a Type III secretion system (based on computational structure prediction and homology search study in C. trachomatis).29 It has high sequence homology with proteins from other Chlamydiae, but does not share homology with proteins from other bacterial genera.30 It is also universally conserved among all C. trachomatis serovars. Therefore, CT584 is a promising target antigen for generating cross-serovar immune responses.

[0090] A Chlamydia sp. CT584 polypeptide includes a native full-length Chlamydia sp. CT584 polypeptide and immunogenic variants thereof. An immunogenic variant of a Chlamydia sp. CT584 polypeptide is capable of eliciting an immune response in an individual, for example, a T-cell response and / or an antibody response (e.g., an antigen-specific T-cell and / or antibody response). The immunogenic variants of CT584 include immunogenic fragments of a Chlamydia sp. CT584 polypeptide. The immunogenic CT584 fragments include fragments of a Chlamydia sp. CT584 polypeptide that are at least 50, at least 75, at least 100, at least 125, at least 150, or at least 175 amino acids long. Typically, the CT584 polypeptide of the invention is a Chlamydia sp. CT584 polypeptide.In certain modalities, immunogenic variants exclude sequence motifs that are found in an individual's proteome (e.g., human), for example, sequence motifs of 8 or more, 9 or more, 10 or more, 11 or more, 12 or more, 13 or more, 14 or more, or 15 or more amino acids in length. The excluded sequence motifs from the individual's proteome (e.g., human proteome) are typically 8 or more amino acids in length. As explained above, this helps minimize unwanted cross-reactivity. Petition 870250077861, dated 01 / 09 / 2025, page 52 / 418 43 / 306

[0091] Exemplary Chlamydia sp. CT584 polypeptide sequences include a Chlamydia trachomatis CT584 polypeptide sequence (see SEQ ID NO: 509). Typically, the Chlamydia sp. CT584 polypeptide of the invention comprises a single amino acid substitution at a position corresponding to residue 11 of SEQ ID NO: 509 (e.g., a substitution from N to Q).

[0092] In some embodiments, the CT584 polypeptide of Chlamydia sp. comprises the sequence of any of the SEQ ID NO: 509-512 (e.g., SEQ ID NO: 510) or a sequence with at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity therewith. In some embodiments, the Chlamydia sp. CT584 polypeptide comprises a sequence with at least 90% identity with any of the SEQ ID NO: 509-512 (e.g., SEQ ID NO: 510). In some embodiments, the Chlamydia sp. CT584 polypeptide... It comprises a sequence with at least 95% identity to any of the SEQ ID NO: 509-512 (for example, SEQ ID NO: 510).

[0093] In some embodiments, a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT584 polypeptide comprises a nucleotide sequence according to any of the SEQ ID NO: 711-718 (e.g., SEQ ID NO: 715) or a sequence that has at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity therewith. In Petition 870250077861, dated 01 / 09 / 2025, page 53 / 418 44 / 306 In some embodiments, the nucleic acid comprises a nucleotide sequence that is at least 85% identical to any of the SEQ ID NO: 711-718 (e.g., SEQ ID NO: 715). In some embodiments, the nucleic acid comprises a nucleotide sequence that encodes a secretion signal peptide sequence as described in this document, for example, a secretion signal peptide sequence according to SEQ ID NO: 187. For example, the nucleic acid may comprise a sequence according to SEQ ID NO: 377.

[0094] In one embodiment, the nucleic acid is an mRNA that comprises or consists of (e.g., consists of) the following structural elements: (1) a chapter 5': (2) an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; (3) a protein coding region having the nucleic acid sequence according to SEQ ID NO: 377 optionally followed by a stop codon (e.g., TGA); (4) an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO:839 and (5) a poly(A) tail.

[0095] In one embodiment, the nucleic acid is an mRNA that comprises or consists of (e.g., consists of) the following structural elements: (1) a chapter 5' with the following structure: THE Petition 870250077861, dated 01 / 09 / 2025, page 54 / 418 45 / 306 (2) an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; (3) a protein-coding region having the nucleic acid sequence according to SEQ ID NO:377; (4) an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO:839 and (5) a poly(A) tail.

[0096] In some embodiments, the 3' end of (1) is directly linked to the 5' end of (2) via a 3' to 5' phosphodiester bond; the 3' end of (2) is directly linked to the 5' end of (3) via a 3' to 5' phosphodiester bond; the 3' end of (3) is directly linked to the 5' end of (4) via a 3' to 5' phosphodiester bond; and the 3' end of (4) is directly linked to the 5' end of (5) via a 3' to 5' phosphodiester bond. In some embodiments, the mRNA is chemically modified, and the chemical modification comprises N1-methylpseudouridine in place of each uridine. The mRNA may be encapsulated in an LNP. CT600

[0097] The C. trachomatis CT600 polypeptide has been shown to induce a robust IgG response when administered as an mRNA expressing the antigen or in the form of a recombinant protein. The inventors also showed that an mRNA encoding the C. trachomatis CT600 polypeptide and a recombinant C. trachomatis CT600 protein were able to induce IFNγ-producing T cells.

[0098] In one aspect, the invention provides a nucleic acid comprising a nucleotide sequence encoding a CT600 polypeptide from Chlamydia sp. In another aspect, the invention provides a polypeptide comprising the amino acid sequence of a Petition 870250077861, dated 01 / 09 / 2025, page 55 / 418 46 / 306 Chlamydia sp. CT600 polypeptide. A Chlamydia sp. CT600 polypeptide for use in the present invention can elicit an antibody response (e.g., IgG) (e.g., an antigen-specific antibody response) in an individual. C. trachomatis CT600 polypeptide administered as an mRNA has been shown to elicit a potent antibody response (e.g., IgG) against C. trachomatis elemental bodies (EBS). The induced antibodies were cross-reactive against EBS from different C. trachomatis serovars. The inventors have demonstrated that the C. trachomatis C600 polypeptides of the invention are suitable vaccine candidates.

[0099] A Chlamydia sp. CT600 polypeptide for use in the present invention can elicit a T cell response (e.g., antigen-specific T cell response) in an individual. In some embodiments, a Chlamydia sp. CT600 polypeptide for use in the invention induces IFNγ-producing T cells, such as IFNγ-producing CD4+ T cells and / or IFNγ-producing CD8+ T cells in an individual.

[00100] CT600 is a peptidoglycan (Pal)-associated lipoprotein from Chlamydia sp., believed to form a cross-bridge between the peptidoglycan and the outer membrane.

[00101] A Chlamydia sp. CT600 polypeptide includes a mature form of a full-length native Chlamydia sp. CT600 polypeptide without its native signal peptide sequence. An immunogenic variant of a native Chlamydia sp. CT600 polypeptide is capable of eliciting an immune response (e.g., an antigen-specific immune response) in an individual, for example, a T-cell response and / or an antibody response. Immunogenic variants of a native Chlamydia sp. CT600 polypeptide include immunogenic fragments of a native Chlamydia sp. CT600 polypeptide. Petition 870250077861, dated 01 / 09 / 2025, page 56 / 418 47 / 306 Chlamydia sp. CT600 immunogenic fragments include fragments of a Chlamydia sp. CT600 polypeptide that are at least 50, at least 75, at least 100, at least 125, or at least 150 amino acids long. Preferred immunogenic fragments of a Chlamydia sp. CT600 polypeptide include fragments lacking the cysteine-rich N-terminal region of a Chlamydia sp. CT600 polypeptide (e.g., fragments lacking the 13 amino acids that immediately follow the native signal peptide of a Chlamydia sp. CT600 polypeptide). In certain modalities, immunogenic fragments exclude sequence motifs that are found in an individual's proteome (e.g., human), for example, sequence motifs of 8 or more, 9 or more, 10 or more, 11 or more, 12 or more, 13 or more, 14 or more, or 15 or more amino acids in length. The excluded sequence motifs from the individual's proteome (e.g., human proteome) typically have 8 or more amino acids in length.As explained above, this helps to minimize unwanted cross-reactivity.

[00102] Exemplary Chlamydia sp. CT600 polypeptide sequences include a Chlamydia trachomatis CT600 polypeptide sequence at SEQ ID NO: 513 that does not have a native Chlamydia trachomatis CT600 polypeptide signal sequence and the 13-amino acid region that immediately follows the signal peptide.

[00103] In some embodiments, the Chlamydia sp. CT600 polypeptide comprises the sequence with SEQ ID NO: 513 or 514 or a sequence with at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity therewith. In some embodiments, the poly Petition 870250077861, dated 01 / 09 / 2025, page 57 / 418 48 / 306 Chlamydia sp. CT600 peptide comprises a sequence with at least 90% identity to any of the SEQ IDs NO. 513-514. In some embodiments, the Chlamydia sp. CT600 polypeptide comprises a sequence with at least 95% identity to any of the SEQ IDs NO. 513-514.

[00104] In some embodiments, a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT600 polypeptide comprises a nucleotide sequence according to any of the SEQ ID NO: 719-722 or a sequence that has at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity therewith. In some embodiments, the nucleic acid comprises a nucleotide sequence that is at least 85% identical to any of the SEQ ID NO: 719-722. CT812

[00105] It has been shown that mRNAs encoding the CT812 polypeptide from C. trachomatis and a recombinant CT812 protein from C. trachomatis induced IFNγ-producing T cells.

[00106] In one aspect, the invention provides a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT812 polypeptide. In another aspect, the invention provides a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT812 polypeptide. A Chlamydia sp. CT812 polypeptide for use in the present invention can elicit an antibody response (e.g., IgG) (e.g., an antigen-specific antibody response) in an individual. A Chlamydia sp. CT812 polypeptide for use in the present invention can Petition 870250077861, dated 01 / 09 / 2025, page 58 / 418 49 / 306 elicit a T cell response (e.g., antigen-specific T cell response) in an individual. In some embodiments, a Chlamydia sp. CT812 polypeptide for use in the invention induces IFNγ-producing T cells, such as IFNγ-producing CD4+ T cells and / or IFNγ-producing CD8+ T cells in an individual.

[00107] CT812 (also called Polymorphic Membrane Protein D (or PmpD)) is a self-transporting protein anchored to the outer membrane of the bacterium Chlamydia sp. CT812 is a proposed adhesin protein. Mature CT812 comprises a passenger domain and a beta-barrel domain.32. Immunization with recombinant CT812 protein has been shown to be protective against serovar D of C. trachomatis in mice.31

[00108] A Chlamydia sp. CT812 polypeptide as used herein includes a mature form of a full-length native Chlamydia sp. CT812 polypeptide without its native signal peptide sequence and immunogenic variants thereof. An immunogenic variant of a Chlamydia sp. CT812 polypeptide is capable of eliciting an immune response (e.g., an antigen-specific immune response) in an individual, for example, a T-cell response and / or an antibody response. Immunogenic variants of a native Chlamydia sp. CT812 polypeptide include immunogenic fragments of a native Chlamydia sp. CT812 polypeptide. Immunogenic CT812 fragments include fragments of a native Chlamydia sp. CT812 polypeptide. who have at least 50, at least 75, at least 100, at least 150, at least 200, at least 250, at least 300, at least 350, at least 400, at least 450, at least 500, at least 550, at least 600, at least 650, at least 700, at least 750, at least 800, at least 850, at least 900, at least 950, at least 1000, at least 1050, at least 1100 or at least Petition 870250077861, dated 01 / 09 / 2025, page 59 / 418 50 / 306 minus 1150 amino acids in length. In some embodiments, immunogenic fragments of a CT812 polypeptide from Chlamydia sp. These include fragments of the amino acid sequence at SEQ ID NO: 515. In some embodiments, the immunogenic fragments may be passenger domain fragments, for example, fragments comprising residues 52-1003 of SEQ ID NO: 515 or residues 52-1179 of SEQ ID NO: 515. In some embodiments, the immunogenic fragments comprise the amino acid sequence according to SEQ ID NOs: 516 or 518. In some embodiments, the passenger domain fragments may be at least 600, at least 650, at least 700, at least 750, at least 800, at least 850, at least 900, at least 950, at least 1000, at least 1050, at least 1100, or at least 1150 amino acids in length.In certain modalities, immunogenic fragments exclude sequence motifs that are found in an individual's proteome (e.g., human), for example, sequence motifs of 8 or more, 9 or more, 10 or more, 11 or more, 12 or more, 13 or more, 14 or more, or 15 or more amino acids in length. The excluded sequence motifs from the individual's proteome (e.g., human proteome) are typically 8 or more amino acids in length. As explained above, this helps minimize unwanted cross-reactivity.

[00109] Exemplary CT812 polypeptide sequences from Chlamydia sp. include a CT812 polypeptide sequence from Chlamydia trachomatis at SEQ ID NO: 515 that does not possess a native signal peptide sequence of the Chlamydia trachomatis CT812 polypeptide. CT812 polypeptide sequences from Chlamydia sp. also include SEQ ID NOs 516 and 518.

[00110] In some embodiments, the CT812 polypeptide of Chlamydia sp. comprises the sequence of any of the SEQ IDs Petition 870250077861, dated 01 / 09 / 2025, p. 60 / 418 51 / 306 NO: 515-535 or a sequence with at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with it. In some embodiments, the Chlamydia sp. CT812 polypeptide comprises a sequence with at least 90% identity with any of the SEQ IDs NO 515-535. In some embodiments, the Chlamydia sp. CT812 polypeptide comprises a sequence with at least 95% identity with any of the SEQ IDs NO 515-535.

[00111] In some embodiments, a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT812 polypeptide comprises a nucleotide sequence according to any of the SEQ ID NO: 723-762 or a sequence that has at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity therewith. In some embodiments, the nucleic acid comprises a nucleotide sequence that is at least 85% identical to any of the SEQ ID NO: 723-762. Modified MOMP polypeptide variants, MOMP VD chimeric polypeptides, and non-MOMP antigen polypeptides

[00112] The modified MOMP polypeptide sequences, the chimeric VD MOMP polypeptides of Chlamydia sp., the CT443 polypeptides of Chlamydia sp., the CT584 polypeptides of Chlamydia sp., the CT600 polypeptides of Chlamydia sp., and / or the CT812 polypeptides of Chlamydia sp., as described herein, may comprise one or more mutations or modifications. Petition 870250077861, dated 01 / 09 / 2025, page 61 / 418 52 / 306

[00113] In some embodiments, the modified MOMP polypeptides, the chimeric VD polypeptides of Chlamydia sp. MOMP, the CT443 polypeptides of Chlamydia sp., the CT584 polypeptides of Chlamydia sp., the CT600 polypeptides of Chlamydia sp. and / or the CT812 polypeptides of Chlamydia sp., as described herein, may comprise one or more conservative amino acid substitutions.

[00114] A conservative amino acid substitution is one in which the amino acid residue is replaced by an amino acid residue possessing a similar side chain. Families of amino acid residues with similar side chains have been defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine), and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine).Thus, if an amino acid in a polypeptide is replaced by another amino acid from the same side chain family, the substitution is considered conservative. In some embodiments, an amino acid chain can be conservatively replaced by a structurally similar chain that differs in the order and / or composition of the side chain family members. Cysteine ​​residue mutation

[00115] One or more cysteine ​​residues in the polypeptides described in this document may be mutated by single amino acid substitutions, for example, at a serine residue. Cysteine ​​residues are involved in disulfide bridge formation and, Petition 870250077861, dated 01 / 09 / 2025, page 62 / 418 53 / 306 Thus, cysteine ​​mutations can limit polypeptide multimerization.

[00116] In some embodiments, a modified MOMP polypeptide described herein comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in a conserved domain sequence of a native Chlamydia sp. MOMP polypeptide. In some embodiments, a chimeric VD MOMP polypeptide described herein may comprise a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in a conserved domain sequence of a native Chlamydia sp. MOMP polypeptide. The conserved domains of native C. trachomatis serovar E MOMP polypeptides comprise Cys residues at positions C48, C51, C55, C124, C137, C204, C206, C229 and / or C357 of SEQ ID NO: 2. The conserved domains of native Chlamydia sp. MOMP polypeptidesThey may include cysteine ​​residues in positions corresponding to the residues defined for the MOMP polypeptide native to serovar E of C. trachomatis.

[00117] In some embodiments, the Chlamydia sp. CT443 polypeptide described herein comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in a native Chlamydia sp. CT443 polypeptide. In some embodiments, the Chlamydia sp. CT443 polypeptide comprises one or more single amino acid substitutions at positions corresponding to C57, C100, C111, C156, C157, C164, C166, C175, C181, C191, C194, C252, C268, C285, C299, C341, C380, C383, C386, C389, C405, C410, C414 and / or C424 of SEQ ID NO: 507. In some embodiments, the Chlamydia sp. polypeptide CT443 comprises one or more Petition 870250077861, dated 01 / 09 / 2025, page 63 / 418 54 / 306 single amino acid substitutions at positions corresponding to C57, C100, C111, C156, C157, C164, C166, C175, C181, C191, C194, C252, C268, C285, C299, C341, C380, C386, C405, C410, C414 and / or C424 of SEQ ID NO: 507. Typically, however, the Chlamydia sp. CT443 polypeptide described herein does not comprise a single amino acid substitution at any position corresponding to a cysteine ​​residue in a native Chlamydia sp. CT443 polypeptide.

[00118] In some embodiments, the Chlamydia sp. CT584 polypeptide described herein comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in a native Chlamydia sp. CT584 polypeptide. In some embodiments, the Chlamydia sp. CT584 polypeptide comprises one or more single amino acid substitutions at positions corresponding to C44, C114, and / or C138 of SEQ ID NO: 509.

[00119] In some embodiments, the Chlamydia sp. CT600 polypeptide described in this document comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in a native Chlamydia sp. CT600 polypeptide. In some embodiments, the Chlamydia sp. CT600 polypeptide comprises one or more (e.g., all) single amino acid substitutions at positions corresponding to C1, C5, C10, and / or C13 of SEQ ID NO: 844.

[00120] In some embodiments, the Chlamydia sp. CT812 polypeptide described in this document comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in a native Chlamydia sp. CT812 polypeptide. In some embodiments, the Chlamydia sp. CT812 polypeptide comprises one or more (e.g., all) positions corresponding to a cysteine ​​residue in a native Chlamydia sp. CT812 polypeptide. Petition 870250077861, dated 01 / 09 / 2025, p. 64 / 418 55 / 306 example, all) single amino acid substitutions at positions corresponding to C1, C96, C160, C169, C179, C187, C233, C291, C300, C331, C348, C365, C401, C432, C560, C570, C571, C641, C665, C756, C838, C859, C963, C980 and / or C1477 of SEQ ID NO: 515. In some embodiments, the Chlamydia sp. polypeptide CT812 comprises one or more (e.g., all) single amino acid substitutions at positions corresponding to C96, C169, C291, C300, C331, C348, C365, C401, C432, C560, C570, C571, C756, C838, C859, C963 and / or C980 of SEQ ID NO: 515. Mutation of glycosylation sites

[00121] Glycosylation can occur in eukaryotic cells (but not in prokaryotic cells). As used in this document, glycosylation refers to the addition of a saccharide unit to a protein. In particular, N-linked glycosylation is the attachment of the glycan to an amide nitrogen of an asparagine (Asn; N) residue of a protein. Glycosylation can occur at any asparagine residue in a protein that is accessible and recognized by glycosylating enzymes after protein translation and is most common in accessible asparagines that are part of an NXS / T motif, where the second amino acid residue after asparagine is a serine (Ser; S) or threonine (Thr; T). O-linked glycosylation is the attachment of a glycan to the oxygen atom of the serine (Ser) or threonine (Thr) residue in a protein. The attachment process results in a glycosylated protein. This glycan could be a polysaccharide.A non-human glycosylation pattern can render a polypeptide undesirably reactogenic when used to induce antibodies. Furthermore, glycosylation of a polypeptide that is not normally glycosylated (such as the polypeptides described herein) can alter its immunogenicity. For example, glycosylation can mask important immunogenic epitopes within a protein. Petition 870250077861, dated 01 / 09 / 2025, page 65 / 418 56 / 306 Thus, to reduce or eliminate glycosylation, asparagus residues or serine / threonine residues can be modified, for example, by substitution with another amino acid.

[00122] In certain embodiments, one or more of the modified MOMP polypeptides, the chimeric VD polypeptide of Chlamydia sp. MOMP, the CT443 polypeptide of Chlamydia sp., the CT584 polypeptide of Chlamydia sp., the CT600 polypeptide of Chlamydia sp., and / or the CT812 polypeptide of Chlamydia sp., as described herein, comprise at least one mutated glycosylation site, preferably at least one mutated N-linked glycosylation site and / or at least one O-linked glycosylation site. In some embodiments, one or more N-glycosylation sites in one or more of the modified MOMP polypeptides, the chimeric VD polypeptide of Chlamydia sp. MOMP, the CT443 polypeptide of Chlamydia sp., the CT584 polypeptide of Chlamydia sp., the CT600 polypeptide of Chlamydia sp. The Chlamydia sp. CT812 polypeptide, as described in this document, is removed. Removal of an N-glycosylation site may decrease the glycosylation of the polypeptide.The removal of a glycosylation site can decrease the glycosylation of the polypeptide. In some embodiments, one or more of the modified MOMP polypeptides, the chimeric VD MOMP polypeptides of Chlamydia sp., the CT443 polypeptide of Chlamydia sp., the CT584 polypeptide of Chlamydia sp., the CT600 polypeptide of Chlamydia sp., and / or the CT812 polypeptide of Chlamydia sp., as described herein, exhibit reduced glycosylation compared to the respective native polypeptide. Removal of the N-glycosylation sites can eliminate the N-glycosylation of the polypeptide. Removal of the O-glycosylation sites can eliminate the O-glycosylation of the polypeptide.

[00123] In certain embodiments, the modification comprises a substitution of one or more amino acids from N, S, and T in a mo Petition 870250077861, dated 01 / 09 / 2025, page 66 / 418 57 / 306 NXS / T sequence type, where X corresponds to any amino acid. In some embodiments, the modification comprises a substitution of one or more serine (Ser) or threonine (Thr) residues in a protein. In some embodiments, an N, S, or T amino acid is replaced by a conservative amino acid substitution. Typically, an N amino acid can be replaced by a Q, S, K, or A amino acid.

[00124] In some embodiments, the chimeric VD MOMP polypeptide described herein comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to an N-glycosylation site in a modified Chlamydia sp. MOMP polypeptide. The N-glycosylation sites in a native Chlamydia sp. MOMP polypeptide may be in one or more MOMP VD domains.N-glycosylation sites may be present at VD1 of MOMP serovar E (position 9 of SEQ ID NO: 9), VD1 of MOMP serovar F (position 11 of SEQ ID NO: 13), VD1 of MOMP serovar G (position 11 of SEQ ID NO: 17), VD2 of MOMP serovar E (position 6 and / or 17 of SEQ ID NO: 10), VD2 of MOMP serovar F (position 4 and / or 21 of SEQ ID NO: 14), VD2 of MOMP serovar D (position 17 of SEQ ID NO: 6); VD2 of MOMP serovar G (position 4 and / or 21 of SEQ ID NO: 18), VD4 of MOMP serovar E (position 14 in SEQ ID NO: 12); VD4 of MOMP serovar G (position 14 in SEQ ID NO: 20); VD4 of MOMP serovar D (position 14 in SEQ ID NO: 8) and / or VD4 of MOMP serovar F (position 14 in SEQ ID NO: 16), wherein the DG serovars are of C. trachomatis.In some embodiments, the chimeric MOMP VD polypeptide comprises (i) a MOMP VD1 sequence from serovar E and a MOMP VD1 sequence from serovar G and (ii) a MOMP VD2 sequence from serovar D and a MOMP VD2 sequence from serovar G and (iii) a MOMP VD3 sequence from serovar F and (iv) a sequence. Petition 870250077861, dated 01 / 09 / 2025, p. 67 / 418 58 / 306 VD4 of MOMP from serovar D and a VD4 sequence of MOMP from serovar F, where serovars D, E, F, or G are from C. trachomatis. Typically, the chimeric polypeptide VD of MOMP comprises a single amino acid substitution at each of the amino acid residues corresponding to position 9 of SEQ ID NO: 9 (e.g., N to A substitution), position 11 of SEQ ID NO: 17 (e.g., T to A substitution), position 17 of SEQ ID NO: 6 (e.g., S to A substitution), positions 4 and 21 of SEQ ID NO: 18 (e.g., N to A and S to A substitutions, respectively), position 14 of SEQ ID NO: 8 (e.g., a T to A substitution), and position 14 in SEQ ID NO: 16 (e.g., T to A substitution).

[00125] In some embodiments, the Chlamydia sp. CT443 polypeptide described in this document comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to an N-glycosylation site in a native Chlamydia sp. CT443 polypeptide. In some embodiments, the Chlamydia sp. CT443 polypeptide comprises one or more (e.g., all) single amino acid substitutions at positions corresponding to residues 18, 29, and 435 of SEQ ID NO: 507.

[00126] In some embodiments, the Chlamydia sp. CT584 polypeptide described herein comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to an N-glycosylation site in a native Chlamydia sp. CT584 polypeptide. Typically, the Chlamydia sp. CT584 polypeptide comprises a single amino acid substitution at a position corresponding to residue 11 of SEQ ID NO: 509 (e.g., an N to Q substitution).

[00127] In some embodiments, the Chlamydia sp. CT600 polypeptide described herein comprises a single Petition 870250077861, dated 01 / 09 / 2025, page 68 / 418 59 / 306 ca amino acid substitution at one or more (e.g., all) positions corresponding to an N-glycosylation site in a native Chlamydia sp. CT600 polypeptide. In some embodiments, the Chlamydia sp. CT600 polypeptide comprises one or two single amino acid substitutions at positions corresponding to residues 48 and 65 of SEQ ID NO: 513.

[00128] In some embodiments, the Chlamydia sp. CT812 polypeptide described in this document comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to an N-glycosylation site in a native Chlamydia sp. CT812 polypeptide. Secretion signal peptide sequences

[00129] The modified MOMP polypeptide, the chimeric VD polypeptide of Chlamydia sp. MOMP, the Chlamydia sp. CT443 polypeptide, the Chlamydia sp. CT584 polypeptide, the Chlamydia sp. CT600 polypeptide, and / or the Chlamydia sp. CT812 polypeptide, as described herein, may comprise a secretion signal peptide sequence. The secretion signal peptide may be cleaved during post-translational processing of the Chlamydia sp. polypeptides described herein. The mature form of the Chlamydia sp. polypeptide may therefore not comprise the secretion signal peptide sequence. However, a nucleotide sequence encoding a secretion signal peptide sequence may be present in nucleic acids described herein that encode the Chlamydia sp. polypeptides described herein.

[00130] The modified MOMP polypeptide, the VD chimeric polypeptide of MOMP from Chlamydia sp., the CT443 polypeptide from Chlamydia sp., the CT584 polypeptide from Chlamydia sp., the CT600 polypeptide from Chlamydia sp. and / or the polypeptide CT812 from Chlamydia sp., as Petition 870250077861, dated 01 / 09 / 2025, page 69 / 418 60 / 306 described in this document may comprise a secretion signal peptide sequence of the respective native Chlamydia sp. polypeptide. This may be advantageous if Chlamydia sp. polypeptides are expressed in a prokaryotic cell as recombinant proteins.

[00131] In some embodiments, the modified MOMP polypeptide, the chimeric VD polypeptide of Chlamydia sp. MOMP, the Chlamydia sp. CT443 polypeptide, the Chlamydia sp. CT584 polypeptide, the Chlamydia sp. CT600 polypeptide, and / or the Chlamydia sp. CT812 polypeptide, as described herein, may comprise viral or eukaryotic (e.g., human) secretion signal peptide (SS) sequences. The use of viral or eukaryotic secretion signal peptide sequences attached to a polypeptide described herein may offer numerous advantages for immunogenic compositions. When expressed from an mRNA, especially in a eukaryotic cell, a polypeptide of the invention comprising an SS sequence may have increased extracellular expression compared to the polypeptide without the SS sequence. Increased extracellular expression may promote greater immunogenicity and, by extension, improved vaccine efficacy.

[00132] Viral SS sequences can be found in publicly accessible databases (e.g., NCBI or UniProt databases) that include an annotated viral polypeptide sequence and identify the start and end positions of an experimentally validated SS.

[00133] In certain embodiments, the SS sequence, as well as the location of the SS sequence cleavage site for a given known input polypeptide sequence, can be predicted using the SignalP algorithm. The SignalP algorithm (and more particularly SignalP v6.0) is described in more detail in Armenteros. Petition 870250077861, dated 01 / 09 / 2025, p. 70 / 418 61 / 306 et al. (Nature Biotechnology. 37: 420-423. 2019), Teufel et al. (Nature Biotechnology. 40: 1023-1025. 2022), and https: / / services.healthtech.dtu.dk / services / SignalP-6.0 / , each of which is incorporated herein in its entirety by reference. Prediction strength is assessed based on a cumulative ranking score that considers the probability of detecting canonical signal sequence features (SS probability score) and the probability of cleavage at the cleavage site (cleavage probability score). In certain embodiments, the viral secretion signal peptide has a SignalP cleavage probability score of at least 0.8, at least 0.85, at least 0.90, or at least 0.95, as determined using SignalP 6.0.In certain embodiments, the viral secretion signal peptide has a SignalP signal peptide probability score of at least 0.8, at least 0.85, at least 0.90, or at least 0.95, as determined using SignalP 6.0.

[00134] In certain embodiments, the SS sequence is a viral SS sequence. In certain embodiments, the viral secretion signal peptide sequence is derived from a viral sequence in a virus capable of infecting humans. The phrase Influenza, SARS COV2, varicella-zoster virus (VZV), measles, rubella, rabies, Ebola, and smallpox preceding the phrase secretion signal peptide sequence indicates that the secretion signal peptide was derived from the virus corresponding to that name.

[00135] In certain embodiments, the viral secretion signal peptide is derived from a viral sequence selected from the group consisting of: an influenza secretion signal peptide sequence, a SARS-CoV-2 secretion signal peptide sequence, a varicella-zoster virus (VZV) secretion signal peptide sequence, a measles secretion signal peptide sequence, Petition 870250077861, dated 01 / 09 / 2025, page 71 / 418 62 / 306 is a rubella secretion peptide sequence, a mumps secretion signal peptide sequence, an Ebola secretion signal peptide sequence, a rabies secretion signal peptide sequence, and a smallpox secretion signal peptide sequence. These specific signal peptides are derived from viral sequences in viruses that have been administered to humans as vaccines (live attenuated, inactivated, or mRNA), with demonstrated strong safety profiles.

[00136] In certain embodiments, the viral secretion signal peptide is selected from the group consisting of: an influenza hemagglutinin (HA) secretion signal peptide sequence, a SARS-CoV-2 spike secretion signal peptide sequence, a VZV gB secretion signal peptide sequence, a VZV gE secretion signal peptide sequence, a VZV gI secretion signal peptide sequence, a VZV gK secretion signal peptide sequence, a measles protein F secretion signal peptide sequence, a rubella protein E1 secretion signal peptide sequence, a rubella protein E2 secretion signal peptide sequence, a mumps protein F secretion signal peptide sequence, an Ebola protein GP secretion signal peptide sequence, a rabies virus glycoprotein (Rabies G) secretion signal peptide sequence, and a 6kDa IC protein secretion signal peptide sequence. smallpox.

[00137] In certain embodiments, the viral secretion signal peptide comprises a secretion signal peptide sequence of influenza A or influenza B HA, preferably influenza A.

[00138] Exemplary viral secretion signal peptide sequences from the description are shown below in Table 2. Exemplary viral secretion signal peptide sequences derived from Petition 870250077861, dated 01 / 09 / 2025, page 72 / 418 63 / 306 influenza A or B from the description are shown below in Table 2.1. Table 2 - Amino Acid Sequences of Viral Secretion Signal (SS) Peptides PROTEIN NAME ORGANISSM STRAIN SEQUENCE OF SS HA (H1N1) Influenza A / New Caledonia / 20 / 1999 Influenza Virus A / New Caledonia / 20 / 1999 MKAKLLVLLCTFTATYA (SEQ ID NO: 187) HA (H1N1pdm) Influenza A / California Virus / 2009 / 9 MKAILVVLLYTFATANA (SEQ ID NO: 188) HA (H3N2) Influenza A / Moscow / 10 / 199 Virus 9 MKTIIALSYILCLVFA (SEQ ID NO: 193) HA B Influenza Virus B / Phuket / 3073 / 20 13 SARSIVA MKATSIVNA (SEQ ID NO: 194) Spike ID CoV-2 Wuhan-1 MFVFLVLLPLVS (SEQ ID NO: 195) Spike SARS CoV-2 Wuhan-1 (long version) MFLLTTKRTMFVFLVLLPLVS (SEQ ID NO: 196) gB ​​VZV Cepa Oka CIFSMFVTAVVS (SEQ ID NO: 803) gE VZV Cepa Oka MGTVNKPVVGVLMGFGIITGTLRITNPVRA (SEQ ID NO: 804) gI VZV Cepa Oka MFLIQCLISAVYIQVTNA (SEQ ID NO: 805) gK VZVSEpa MGCHAIQA GQHAIQ ID NO: 806) F Measles Strain EdmonstonZagreb MGLKVNVSAIFMAVLLTLQTPTG (SEQ ID NO: 807) E1 Rubelola Strain RA27 / 3 MGAAAALTAVVLQGYNPPAYG (SEQ ID NO: 808) Petition 870250077861, of 01 / 09 / 2025, p. 73 / 418 64 / 306 E2 Rubella Strain RA27 / 3 MGAPQAFLAGLLLAA- VAVGTARA (SEQ ID NO: 809) 6kDa IC Smallpox Strain Germany 91-3 MRSLIIFLLFPSIIYS (SEQ ID NO: 812) Rabies G Rabies Strain Rabies Pasteur MVPQALLFVPLLVFPLCFG (SEQ ID NO: 845) Table 2.1 - Amino Acid Sequences of Signal Peptide Specific Viral Secretions (SS) of Influenza A and B viruses NAME OR ID OF THE STRAIN SS SEQUENCE Virus similar to A / Beijing / 262 / 95 (H1N1) to MKAKLLVLLCTFTATYA (SEQ ID NO: 187) Virus similar to A / Brisbane / 02 / 2018 (H1N1)pdm09 to MKAILVVLLYTFTTANA (SEQ ID NO: 846) Virus similar to A / Brisbane / 59 / 2007 (H1N1) to MKVKLLVLLCTFTATYA (SEQ ID NO: 847) Virus similar to A / California / 7 / 2009 (H1N1) to MKAILVVLLYTFATANA (SEQ ID NO: 188) Virus similar to A / GuangdongMaonan / SWL1536 / 2019 (H1N1)pdm09 to MKAILVVLLYTFTTANA (SEQ ID NO: 846) Virus similar to A / Hawaii / 70 / 2019 (H1N1)pdm09 to MKAILVVLLYTFTTANA (SEQ ID NO: 846) Virus similar to A / Michigan / 45 / 2015 (H1N1)pdm09 to MKAILVVLLYTFTTANA (SEQ ID NO: 846) Virus similar to A / New Caledonia / 20 / 99 (H1N1) MKAKLLVLLCTFTATYA (SEQ ID NO: 187) Petition 870250077861, dated 01 / 09 / 2025, page 74 / 418 65 / 306 Virus similar to A / Solomon Islands / 3 / 20C (H1N1) to 6 MKVKLLVLLCTFTATYA (SEQ ID NO: 847) Virus similar to A / Sydney / 5 / 2021 (H1N1)pdm09 to MKAILVVMLYTFTTANA (SEQ ID NO: 848) Virus similar to A / Victoria / 2570 / 2019 (H1N1)pdm09 to MKAILVVMLYTFTTANA (SEQ ID NO: 848) Virus similar to A / Victoria / 4897 / 2022 (H1N1)pdm09 to MKAILVVMLYTFTTANA (SEQ ID NO: 848) Virus similar to A / Wisconsin / 588 / 2019 (H1N1)pdm09 to MKAILVVMLYTFTTANA (SEQ ID NO: 848) Virus similar to A / Wisconsin / 67 / 2022 (H1N1)pdm09 to MKAILVVMLYTFTTANA (SEQ ID NO: 848) H1N1 CONSENSUS SEQ #1 (no replacements) MKAILVVLLYTFTTANA (SEQ ID NO: 846) Virus similar to A / Brisbane / 10 / 2007 (H3N2) to MKTIIALSYILCLVFT 849) (SEQ ID NO: Virus similar to A / California / 7 / 2004 (H3N2) to MKTIIALSYILCLVFA 193) (SEQ ID NO: Virus similar to A / Cambodia / e0826360 / 2020 (H3N2) MKTIIALSYILCLVFA 193) (SEQ ID NO: Virus similar to A / Darwin / 6 / 2021 (H3N2) a MKTIIALSNILCLVFA 850) (SEQ ID NO: Virus similar to A / Darwin / 9 / 2021 (H3N2) a MKTIIALSNILCLVFA 850) (SEQ ID NO: VirusSimilar to A / Fujian / 411 / 2002 (H3N2) MKTIIALSYILCLVFA 193) (SEQ ID NO: Virus similar to A / Hong Kong / 2671 / 2019 (H3N2) MKAIIALSNILCLVFA 851) (SEQ ID NO: Virus similar to A / Hong Kong / 45 / 2019 (H3N2) MKAIIALSNILCLVFA 851) (SEQ ID NO: Virus similar to A / Hong Kong / 4801 / 2014 (H3N2) MKTIIALSYILCLVFA 193) (SEQ ID NO: Petition 870250077861, dated 01 / 09 / 2025, page 75 / 418 66 / 306 Virus similar to A / Kansas / 14 / 2017 (H3N2) MKTIIALSCILCLVFA (SEQ ID NO: 852) Virus similar to A / Moscow / 10 / 99 (H3N2) MKTIIALSYILCLVFA (SEQ ID NO: 193) Virus similar to A / Perth / 16 / 2009 (H3N2) MKTIIALSYILCLVFA (SEQ ID NO: 193) Virus similar to A / Singapore / INFIMH-160019 / 2016 (H3N2) MKTIIALSYILCLVFA (SEQ ID NO: 193) Virus similar to A / South Australia / 34 / 2019 (H3N2) MKTIIALSYILCLVFA (SEQ ID NO: 193) Virus similar to A / Switzerland / 8060 / 2017 (H3N2) MKTIIALSYILCLVFA (SEQ ID NO: 193) Virus similar to A / Switzerland / 9715293 / 2013 (H3N2) MKTIIALSYILCLVFA (SEQ ID NO: 193) Virus similar to A / Sydney / 5 / 97 (H3N2) MKTIIALSYILCLVFA (SEQ ID NO: 193) Virus similar to A / Texas / 50 / 2012 (H3N2) MKTIIALSYILCLVFA (SEQ ID NO: 193) Virus similar to A / Victoria / 361 / 2011 (H3N2) MKTIIALSHILCLVFA (SEQ ID NO: 853) Virus similar to A / Wellington / 1 / 2004 (H3N2) MKTIIALSYILCLVFA (SEQ ID NO: 193) Virus similar to A / Wisconsin / 67 / 2005 (H3N2) MKTIIALSYILCLVFA (SEQ ID NO: 193) H3N2 CONSENSUS SEQ #1 (withoutreplacements) MKTIIALSYILCLVFA (SEQ ID NO: 193) Similar to B / Austria / 1359417 / 2021 (B / Victoria lineage) MKAIIVLLMVVTSNA (SEQ ID NO: 194) Virus similar to B / Brisbane / 60 / 2008 MKAIIVLLMVVTSNA (SEQ ID NO: 194) Virus similar to B / Colorado / 06 / 2017 (B / Victoria / 2 / 87 lineage) MKAIIVLLMVVTSSA (SEQ ID NO: 854) Virus similar to B / Hong Kong / 330 / 2001 MKAIIVLLMVVTSNA (SEQ ID NO: 194) Petition 870250077861, dated 01 / 09 / 2025, page 76 / 418 67 / 306 B / Malaysia / 2506 / 2004-like virus MKAIIVLLMVVTSNA (SEQ ID NO: 194) ID NO: 194) B / Florida / 4 / 2006-like virus MKAIIVLLMVVTSNA (SEQ ID NO: 194) B / Massachusetts / 2 / 2012-like virus MKAIIVLLMVVTSNA (SEQ ID NO: 194) B / Phuket / 3073 / 2013-like virus MKAIIVLLMVVTSNA (SEQ ID NO: 194) Virus similar to B / Sichuan / 379 / 99 MEAIIVLLMVVTSNA (SEQ ID NO: 855) VICTORIA / YAMAGATA INFLUENZA B CONSENSUS SEQUENCE (without substitutions) MKAIIVLLMVVTSNA (SEQ ID NO: 194) H1N1 CONSENSUS SEQUENCE #2 (with substitutions) MKXi X2LX3VX4LX5TFX6X7X8X9A X1 is selected from A and V; X2 is selected from I and K; X3 is selected from V and L; X4 is selected from L and M; X5 is selected from Y and C; X6 is selected from T and A; X7 is selected from T and A; X8 is selected from A and T;X9 is selected from N and Y (SEQ ID NO: 856) H3N2 CONSENSUS SEQ #2 (with substitutions) MKX1IIALSX2ILCLVFX3 X1 is selected from T and A; X2 is selected from Y, N, C and H; and X3 is selected from T and A (SEQ ID NO: 857) INFLUENZA B VICTORIA CONSENSUS SEQ (with substitutions) MKAIIVLLMVVTSXiA Xi is selected from S and N (SEQ ID NO: 858) INFLUENZA B YAMAGATA CONSENSUS SEQ (with substitutions) MX1AIIVLLMVVTSNA X1 is selected from K and E (SEQ ID NO: 859); Petition 870250077861, dated 01 / 09 / 2025, p. 77 / 418 68 / 306

[00139] The secretion signal peptide sequence can be positioned at the N-terminal or C-terminal (e.g., at the N-terminal) of a polypeptide described in this document.

[00140] In certain embodiments, the amino acid sequence of SS is encoded by a codon-optimized polynucleotide sequence.

[00141] In certain embodiments, the viral secretion signal peptide is derived from a viral sequence in a virus with the ability to infect humans.

[00142] In certain embodiments, the viral secretion signal peptide is derived from a viral sequence selected from the group consisting of: an influenza secretion signal peptide sequence and a non-influenza secretion signal peptide sequence selected from the group consisting of a SARS-CoV-2 secretion signal peptide sequence, a varicella-zoster virus (VZV) secretion signal peptide sequence, a measles secretion signal peptide sequence, a rubella secretion signal peptide sequence, a mumps secretion signal peptide sequence, an Ebola secretion signal peptide sequence, a smallpox secretion signal peptide sequence, and a rabies secretion signal peptide sequence.

[00143] In certain embodiments, the viral secretion signal peptide is selected from the group consisting of: an influenza hemagglutinin (HA) secretion signal peptide sequence, a SARS-CoV-2 spike secretion signal peptide sequence, a VZV gB secretion signal peptide sequence, a VZV gE secretion signal peptide sequence, a VZV gI secretion signal peptide sequence, a VZV gK secretion signal peptide sequence, a measles F protein secretion signal peptide sequence, a secretion signal peptide sequence Petition 870250077861, dated 01 / 09 / 2025, page 78 / 418 69 / 306 of rubella E1 protein, a rubella E2 protein secretion signal peptide sequence, a mumps F protein secretion signal peptide sequence, an Ebola GP protein secretion signal peptide sequence, a smallpox 6kDa IC protein secretion signal peptide sequence, and a rabies G protein secretion signal peptide sequence, preferably wherein the viral secretion signal peptide comprises an influenza A or influenza B HA secretion signal peptide sequence, more preferably influenza A.

[00144] In certain embodiments, the HA secretion signal peptide sequence comprises an amino acid sequence MKX1X2LX3VX4LX5TFX6X7X8X9A (SEQ ID NO: 856) wherein X1 is selected from A and V; X2 is selected from I and K; X3 is selected from V and L; X4 is selected from L and M; X5 is selected from Y and C; X6 is selected from T and A; X7 is selected from T and A; X8 is selected from A and T; and X9 is selected from N and Y.

[00145] In certain embodiments, the HA secretion signal peptide sequence comprises an amino acid sequence selected from MKAKLLVLLCTFTATYA (SEQ ID NO: 187), MKAILVVLLYTFTTANA (SEQ ID NO: 846), MKVKLLVLLCTFTATYA (SEQ ID NO: 847), MKAILVVLLYTFATANA (SEQ ID NO: 188) and MKAILVVMLYTFTTANA (SEQ ID NO: 848).

[00146] In certain embodiments, the HA secretion signal peptide sequence comprises an amino acid sequence MKX1IIALSX2ILCLVFX3 (SEQ ID NO: 857) in which X1 is selected from T and A; X2 is selected from Y, N, C and H; and X3 is selected from T and A.

[00147] In certain embodiments, the HA secretion signal peptide sequence comprises an amino acid sequence selected from MKTIIALSYILCLVFT (SEQ ID NO: 849), MKTIIALSYILCLVFA Petition 870250077861, dated 01 / 09 / 2025, page 79 / 418 70 / 306 (SEQ ID NO: 193), MKTIIALSNILCLVFA (SEQ ID NO: 850), MKAIIALSNILCLVFA (SEQ ID NO: 851), MKTIIALSCILCLVFA (SEQ ID NO: 852) and MKTIIALSHILCLVFA (SEQ ID NO: 853).

[00148] In certain embodiments, the HA secretion signal peptide sequence comprises an amino acid sequence MKAIIVLLMVVTSX1A (SEQ ID NO: 858) where X1 is selected between S and N.

[00149] In certain embodiments, the HA secretion signal peptide sequence comprises an amino acid sequence MX1AIIVLLMVVTSNA (SEQ ID NO: 859) where X1 is selected between K and E.

[00150] In certain embodiments, the HA secretion signal peptide sequence comprises an amino acid sequence selected from MKAIIVLLMVVTSNA (SEQ ID NO: 194), MKAIIVLLMVVTSSA (SEQ ID NO: 854) and MEAIIVLLMVVTSNA (SEQ ID NO: 855).

[00151] In certain embodiments, the viral secretion signal peptide comprises an amino acid sequence selected from the group consisting of: MKAKLLVLLCTFTATYA (SEQ ID NO: 187); MKAILVVLLYTFATANA (SEQ ID NO: 188); MKTIIALSYILCLVFA (SEQ ID NO: 193); MKAIIVLLMVVTSNA (SEQ ID NO: 194); MFVFLVLLPLVS (SEQ ID NO: 195); MFLLTTKRTMFVFLVLLPLVS (SEQ ID NO: 196) MSPCGYYSKWRNRDRPEYRRNLRFRRFFSSIHPNAAAGSGFNGPGVFITSVTGVWLCFLCIFSMFVTAVVS (SEQ ID NO: 803); MGTVNKPVVGVLMGFGIITGTLRITNPVRA (SEQ ID NO: 804); MFLIQCLISAVIFYIQVTNA (SEQ ID NO: 805); MQALGIKTEHFIIMCLLSGHA (SEQ ID NO: 806); MGLKVNVSAIFMAVLLTLQTPTG (SEQ ID NO: 807); MGAAAALTAVVLQGYNPPAYG (SEQ ID NO: 808); MGAPQAFLAGLLLAAVAVGTARA (SEQ ID NO: 809); MKVFLVTCLGFAVFSSSVC (SEQ ID NO: 810); Petition 870250077861, dated 01 / 09 / 2025, page 80 / 418 71 / 306 MGVTGILQLPRDRFKRTSFFLWVIILFQRTFS (SEQ ID NO: 811); MRSLIIFLLFPSIIYS (SEQ ID NO: 812) and MVPQALLFVPLLVFPLCFG (SEQ ID NO: 845).

[00152] In certain embodiments, the viral secretion signal peptide comprises an amino acid sequence of MKAKLLVLLCTFTATYA (SEQ ID NO: 187).

[00153] In certain embodiments, the viral secretion signal peptide is positioned at the N-terminal of the antigenic prokaryotic polypeptide. In certain embodiments, the viral secretion signal peptide is positioned at the N-terminal of the polypeptide described in this document.

[00154] In certain embodiments, the viral secretion signal peptide is positioned at the C-terminal of the antigenic prokaryotic polypeptide. In certain embodiments, the viral secretion signal peptide is positioned at the C-terminal of the polypeptide described in this document.

[00155] In certain embodiments, the viral secretion signal peptide is linked to the antigenic prokaryotic polypeptide with a ligand. In certain embodiments, the viral secretion signal peptide is linked to the polypeptide described in this document with a ligand. Heterologous transmembrane domains (TMBs)

[00156] The chimeric polypeptide VD of Chlamydia sp. MOMP, the polypeptide CT443 of Chlamydia sp., the polypeptide CT584 of Chlamydia sp., the polypeptide CT600 of Chlamydia sp., and / or the polypeptide CT812 of Chlamydia sp., as described herein, may comprise a heterologous transmembrane domain. The inclusion of a TMB may be advantageous as it will localize the antigen to the cell membrane. This may reduce the intracellular localization of the antigen and promote even greater immunogenicity compared to the antigen without the TMB sequence. The chimeric polypeptide VD of Chlamydia sp. MOMP, the polypeptide CT443 of Chlamydia sp., the polypeptide CT584 of Chlamydia sp., the polypeptide CT600 of Chlamydia sp. Petition 870250077861, dated 01 / 09 / 2025, page 81 / 418 72 / 306 and / or the Chlamydia sp. polypeptide CT812 comprising a heterologous transmembrane domain may also comprise a secretion signal peptide sequence. Typically, a nucleic acid described herein encoding the chimeric polypeptide VD of Chlamydia sp. MOMP comprising a heterologous transmembrane domain also comprises a nucleotide sequence encoding a secretion signal peptide sequence. Typically, a nucleic acid described herein encoding the Chlamydia sp. polypeptide CT443 comprising a heterologous transmembrane domain also comprises a nucleotide sequence encoding a secretion signal peptide sequence. Typically, a nucleic acid described herein encoding the Chlamydia sp. polypeptide CT584 comprising a heterologous transmembrane domain also comprises a nucleotide sequence encoding a secretion signal peptide sequence.Typically, a nucleic acid described in this document that encodes the CT600 polypeptide of Chlamydia sp. comprising a heterologous transmembrane domain also comprises a nucleotide sequence that encodes a secretion signal peptide sequence. Typically, a nucleic acid described in this document that encodes the CT812 polypeptide of Chlamydia sp. comprising a heterologous transmembrane domain also comprises a nucleotide sequence that encodes a secretion signal peptide sequence.

[00157] The TMB can be any TMB known in the art, including, but not limited to, TMBs of eukaryotic transmembrane proteins (e.g., mammalian transmembrane proteins such as human transmembrane proteins), TMBs of prokaryotic transmembrane proteins, and TMBs of viral transmembrane proteins. TMBs can be identified through predictive algorithms in Petition 870250077861, dated 01 / 09 / 2025, page 82 / 418 73 / 306 silico, for example, in the TMHMM prediction method described in Krogh et al. (J mol Biol. 305(3): 567-580. 2001) and https: / / services.healthtech.dtu.dk / services / TMHMM-2O / , each of which is incorporated herein in its entirety by reference. Some characteristics of TMBs are described in further detail in Albers et al. (Chapter 2 - Cell membrane structures and functions. Basic Neurochemistry eighth edition. Pages 26-39. 2012), incorporated herein in its entirety by reference. TMBs are typically, but not exclusively, comprised predominantly of nonpolar (hydrophobic) amino acid residues and may cross a lipid bilayer one or more times. Those knowledgeable are well acquainted with methods for determining the hydrophobicity of an amino acid. See Simm et al. (2016), Biol Res., 49(1):31; Wimlet and White (1996), Nat Struct Biol., 3(10): 842-848; https: / / blanco.biomol.uci.edu / hydrophobicity_scales.html; and https: / / www.cgl.ucsf.edu / chimera / docs / UsersGuide / midas / hydrophob.h tml.

[00158] TMBs generally comprise alpha helices, where each helix contains 18-21 amino acids, which is sufficient to span the lipid bilayer. Consequently, in certain embodiments, the transmembrane domain comprises one or more alpha helices. In some embodiments, the TMB: (a) comprises or consists of 15 to 50 amino acid residues, preferably 15 to 30 amino acid residues, more preferably 18 to 25 amino acid residues; and / or (b) comprises at least 50%, at least 55%, or at least 60% of hydrophobic amino acid residues, preferably selected from the group consisting of: alanine, isoleucine, leucine, valine, phenylalanine, tryptophan, and tyrosine; and / or (c) comprises at least one alpha helix. Petition 870250077861, dated 01 / 09 / 2025, p. 83 / 418 74 / 306

[00159] In certain embodiments, the transmembrane domain is derived from an integral membrane protein, as defined later and in Albers et al., an integral membrane protein (also known as an intrinsic membrane protein) is a membrane protein that is permanently attached to the lipid membrane. In certain embodiments, the transmembrane domain is derived from an integral polytopic protein. An integral polytopic protein is one that spans the entire membrane. In certain embodiments, the transmembrane domain is derived from a single-pass (trans) membrane protein, more particularly a bitopic membrane protein, for example, of Type I or Type II. Single-pass membrane proteins cross the membrane only once (i.e., a bitopic membrane protein), while multi-pass membrane proteins intertwine inwards and outwards, crossing multiple times.Single-pass transmembrane proteins can be categorized as Type I, which are positioned so that their carboxyl-terminal is towards the cytosol, or Type II, which have their amino-terminal towards the cytosol. In certain embodiments, the transmembrane domain is derived from an integral monotopic protein. An integral monotopic protein is one that is associated with the membrane on only one side and does not completely span the lipid bilayer.

[00160] In certain embodiments, the heterologous transmembrane domain is derived from a non-human sequence.

[00161] In certain embodiments, the heterologous transmembrane domain is derived from a viral sequence. The phrase influenza, SARS COV-2, varicella-zoster virus (VZV), measles, rubella, rabies, Ebola, and smallpox preceding the phrase transmembrane domain sequence indicates that the transmembrane domain sequence was derived from the virus corresponding to that name.

[00162] In certain modalities, the heteromembrane transmembrane domain Petition 870250077861, dated 01 / 09 / 2025, page 84 / 418 The 75 / 306 logo is derived from a viral transmembrane domain sequence selected from the group consisting of: an influenza transmembrane domain sequence, a SARS-CoV-2 transmembrane domain sequence, a varicella-zoster virus (VZV) transmembrane domain sequence, a measles transmembrane domain sequence, a rubella transmembrane domain sequence, a mumps transmembrane domain sequence, a rabies transmembrane domain sequence, and an Ebola transmembrane domain sequence. These specific transmembrane domains are derived from viral sequences in viruses that have been administered to humans as vaccines (live attenuated, inactivated, or mRNA), with demonstrated strong safety profiles.

[00163] In certain embodiments, the heterologous transmembrane domain is selected from the group consisting of: an influenza hemagglutinin (HA) transmembrane domain sequence, a SARS CoV-2 spike transmembrane domain sequence, a VZV gB transmembrane domain sequence, a VZV gE transmembrane domain sequence, a VZV gI transmembrane domain sequence, a VZV gK transmembrane domain sequence, a measles F protein transmembrane domain sequence, a rubella E1 protein transmembrane domain sequence, a rubella E2 protein transmembrane domain sequence, a mumps F protein transmembrane domain sequence, a rabies virus glycoprotein (Rabies G) transmembrane domain sequence, and an ebola GP protein transmembrane domain sequence.

[00164] In certain embodiments, the heterologous transmembrane domain comprises an HA transmembrane domain sequence from influenza A or influenza B, preferably from influenza A.

[00165] Transmembrane domain amino acid sequences Petition 870250077861, dated 01 / 09 / 2025, page 85 / 418 76 / 306 viral examples of the description are shown below in Table 3. Table 3 - Viral Transmembrane Domain (TMB) Signal Amino Acid Sequences PROTEIN NAME ORGANISSM STRAIN TMB SEQUENCE HA (H1N1) Influenza A / New Caledonia Virus / 20 / 1999 ILAIYSTVAS SLVLLVSLGAISF (SEQ ID NO: 813) HA (H1N1pdm) Influenza Virus / California / 2007 / 2009 ILAIYSTVAS SLVLVVSLGAISF (SEQ ID NO: 814) HA (H3N2) Influenza A / Moscow / 10 / 1 999 ILWISFAISCFLLCVVLLGFI (SEQ ID NO: 815) HA B Influenza Virus B / Phuket / 3071 / 3 (SEQ ID NO: 816) Spike SARS CoV- 2 Wuhan-1 WYIWLGFIAGLIAI- VMVTIML (SEQ ID NO: 817) gB VZV Cepa Oka FGALAVGLLVLAGLVAAFFAY (SEQ ID NO: 818) gE VZV Cepa Oka AAWTG (IDGLAAVCL NO: 818) 819) gI VZV Cepa Oka IIIPIVASVMILTAMVIVIVI (SEQ ID NO: 820) gK VZV Cepa Oka YFWCVQLKMIFFAWFVYGMYL (SEQ ID NO: 821) F Sarampo Cepa Edmonston-Zagreb IVYILIAVCLGGGLIGIP Rubé QEALI ID: 822 EOC) RA27 / 3 LDHAFAAFVLLVPWVLIFMVC (SEQ ID NO: 823) E2 Rubella Strain RA27 / 3 WWQLTLGAICALLLAGLLACC (SEQ ID NO: 824) F Caxumba Strain Miyahara IVAALVLSILSIIISLLFCW (SEQ ID NO: 825) Petition 870250077861, of 01 / 09 / 2025, p. 86 / 418 77 / 306 GP Ebola Strain Mayinga76 WIPAGIGVTGVIIAVIALFCI (SEQ ID NO: 826) Rabies G Rabies Strain Rabies Pasteur VLLSAGALTALMLIIFLMTCW (SEQ ID NO: 860)

[00166] In certain embodiments, the heterologous TMB sequence is positioned at the N-terminal or C-terminal (e.g., C-terminal) of a polypeptide described in this document.

[00167] In certain embodiments, the amino acid sequence of TMB is encoded by a codon-optimized polynucleotide sequence.

[00168] In some embodiments, the MOMP VD chimeric polypeptide comprises a heterologous transmembrane domain, as described in this document. In some embodiments, the heterologous transmembrane domain does not comprise the SEQ ID NO: 189 sequence. In some embodiments, the heterologous transmembrane domain comprises the SEQ ID NO: 190 sequence. Typically, the MOMP VD chimeric polypeptide does not comprise a heterologous transmembrane domain.

[00169] In alternative embodiments, one or more of the chimeric polypeptide VD of MOMP, the polypeptide CT443 of Chlamydia sp., the polypeptide CT584 of Chlamydia sp., the polypeptide CT600 of Chlamydia sp., and / or the polypeptide CT812 of Chlamydia sp., as described herein, do not comprise a heterologous transmembrane domain. Such polypeptides may comprise a secretion signal peptide sequence. In further embodiments, the polypeptides of the invention are secreted. In some embodiments, the chimeric polypeptide VD of MOMP described herein is a secreted polypeptide. In some embodiments, the polypeptide CT443 of Chlamydia sp. described herein is a secreted polypeptide. In some embodiments, the polypeptide Petition 870250077861, dated 01 / 09 / 2025, page 87 / 418 78 / 306 CT584 from Chlamydia sp. described in this document is a secreted polypeptide. In some embodiments, the CT600 polypeptide from Chlamydia sp. described in this document is a secreted polypeptide. In some embodiments, the CT812 polypeptide from Chlamydia sp. described in this document is a secreted polypeptide. In preferred embodiments, the modified MOMP polypeptide described in this document is a secreted polypeptide. The secreted polypeptides described in this document comprise a secretory signal peptide sequence.

[00170] In certain embodiments, the TMB: (a) comprises or consists of 15 to 50 amino acid residues, preferably 15 to 30 amino acid residues, more preferably 18 to 25 amino acid residues; and / or (b) comprises at least 50% hydrophobic amino acid residues, preferably selected from the group consisting of: alanine, isoleucine, leucine, valine, phenylalanine, tryptophan and tyrosine; and / or (c) comprises at least one alpha helix.

[00171] In certain embodiments, TMB is derived from an integral membrane protein, preferably from a single-pass membrane protein, more preferably from a bitopic membrane protein, and even more preferably from a Type I bitopic membrane protein.

[00172] In certain modalities, the TMB is derived from a non-human sequence.

[00173] In certain modalities, the TMB is derived from a viral sequence.

[00174] In certain embodiments, the TMB is derived from a viral transmembrane domain sequence selected from the group consisting of: an influenza transmembrane domain sequence, and a non-influenza transmembrane domain sequence selected Petition 870250077861, dated 01 / 09 / 2025, page 88 / 418 79 / 306 is included among the group consisting of a SARS-CoV-2 transmembrane domain sequence, a varicella-zoster virus (VZV) transmembrane domain sequence, a measles transmembrane domain sequence, a rubella transmembrane domain sequence, a mumps transmembrane domain sequence, an Ebola transmembrane domain sequence, and a rabies transmembrane domain sequence.

[00175] In certain embodiments, the TMB is selected from the group consisting of: an influenza hemagglutinin (HA) transmembrane domain sequence, a SARS CoV-2 spike transmembrane domain sequence, a VZV gB transmembrane domain sequence, a VZV gE transmembrane domain sequence, a VZV gI transmembrane domain sequence, a VZV gK transmembrane domain sequence, a measles F protein transmembrane domain sequence, a rubella E1 protein transmembrane domain sequence, a rubella E2 protein transmembrane domain sequence, a mumps F protein transmembrane domain sequence, an Ebola GP protein transmembrane domain sequence, and a rabies G protein transmembrane domain sequence, preferably wherein the TMB comprises an influenza A or influenza B HA transmembrane domain sequence, more preferably influenza A.

[00176] In certain embodiments, TMB comprises an amino acid sequence selected from the group consisting of: ILAIYSTVASSLVLLVSLGAISF (SEQ ID NO: 813); ILAIYSTVASSLVLVVSLGAISF (SEQ ID NO: 814); ILWISFAISCFLLCVVLLGFI (SEQ ID NO: 815); STAASSLAVTLMLAIFIVYMV (SEQ ID NO: 816); WYIWLGFIAGLIAIVMVTIML (SEQ ID NO: 817); FGALAVGLLVLAGLVAAFFAY (SEQ ID NO: 818); AAWTGGLAAVVLLCLVIFLIC (SEQ ID NO: 819); Petition 870250077861, dated 01 / 09 / 2025, p. 89 / 418 80 / 306 IIIPIVASVMILTAMVIVIVI (SEQ ID NO: 820); YFWCVQLKMIFFAWFVYGMYL (SEQ ID NO: 821); IVYILIAVCLGLIGIPALIC (SEQ ID NO: 822); LDHAFAAFVLLVPWVLIFMVC (SEQ ID NO: 823); WWQLTLGAICALLLAGLLACC (SEQ ID NO: 824); IVAALVLSILSIIISLLFCCW (SEQ ID NO: 825); WIPAGIGVTGVIIAVIALFCI (SEQ ID NO: 826) and VLLSAGALTALMLIIFLMTCW (SEQ ID NO: 860).

[00177] In certain embodiments, the TMB comprises the sequence ILAIYSTVASSLVLLVSLGAISF (SEQ ID NO: 813).

[00178] In certain embodiments, TMB is attached to a polypeptide described in this document with a linker.

[00179] In certain embodiments, TMB is positioned at the N-terminal of a polypeptide described in this document.

[00180] In certain embodiments, TMB is positioned at the C-terminal of a polypeptide described in this document. Binders

[00181] In certain embodiments of the description, the secretion signal peptide (SS) sequence or the transmembrane domain (TMB) is directly fused to a polypeptide described herein (i.e., there is no linker, such as an amino acid linker, connecting the SS or TMB sequence to the polypeptide described herein).

[00182] In other embodiments, the SS and TMB sequences of the description are optionally attached to a polypeptide described in this document with a linker. In certain embodiments, the linker is an amino acid linker. In certain embodiments, the amino acid linker is 1-10 amino acids long (e.g., the amino acid linker is 1 amino acid long, 3 amino acids long, 4 amino acids long, 2 amino acids long, 5 amino acids long, 6 amino acids long, 7 amino acids long, 8 amino acids long, 9 amino acids long, or 10 amino acids long). Petition 870250077861, dated 01 / 09 / 2025, p. 90 / 418 81 / 306

[00183] Illustrative examples of linkers include glycine (Gly)n polymers, wherein n is an integer of at least one, two, three, four, five, six, seven, or eight; glycine-serine (GlySer)n polymers, wherein n is an integer of at least one, two, three, four, five, six, seven, or eight; glycine-alanine polymers; alanine-serine polymers; and other flexible linkers known in the art.

[00184] Glycine and glycine-serine polymers are relatively unstructured and flexible, therefore they may have the ability to serve as a neutral linker between the SS and / or TMB sequence and the polypeptides described herein. In certain embodiments, the linker is SGS or GSG.

[00185] Other exemplary ligands include, but are not limited to, the following amino acid sequences: GGG; DGGGS (SEQ ID NO: 827); TGEKP (SEQ ID NO: 828) (Liu et al. Proc. Natl. Acad. Sci. 94: 5525-5530. 1997); GGRR (SEQ ID NO: 829); (GGGGS)n (SEQ ID NO: 830), where n = 1, 2, 3, 4 or 5 (Kim et al. Proc. Natl. Acad. Sci. 93: 1156-1160. 1996); EGKSSGSGSESKVD (SEQ ID NO: 831) (Chaudhary et al. Proc. Natl. Acad. Sci. 87: 1066-1070. 1990); KESGSVSSEQLAQFRSLD (SEQ ID NO: 832) (Bird et al. Science. 242:423-426. 1988), GGRRGGGS (SEQ ID NO: 833); LRQRDGERP (SEQ ID NO: 834); LRQKDGGGSERP (SEQ ID NO: 835); and GSTSGSGKPGSGEGSTKG (SEQ ID NO: 836) (Cooper et al. Blood. 101(4): 1637-1644. 2003). Preferred ligands are shorter, for example, consisting of 3, 4, or 5 amino acids.

[00186] Additional examples of ligands are provided in Chen et al. (Adv Drug Deliv Rev. 65(10): 1357-1369. 2013), incorporated herein in its entirety by reference. Compositions

[00187] The invention provides a composition comprising one or more nucleic acids of the description. The invention also provides Petition 870250077861, dated 01 / 09 / 2025, p. 91 / 418 82 / 306 a composition comprising one or more polypeptides of the description. A composition of the invention may be a pharmaceutical composition, for example, comprising a pharmaceutically acceptable vehicle, excipient or diluent. In certain embodiments, the composition of the invention is an immunogenic composition. An immunogenic composition means a composition comprising a nucleic acid or protein which, when administered to an individual, elicits an immune response, for example, an antigen-specific immune response. The response may be a T-cell immune response or an antibody response. The composition of the invention may be a vaccine composition. Immunogenic compositions (e.g., vaccine compositions) may elicit protective immunity (e.g., T-cell and / or B-cell responses (i.e., antibodies)) against infection by Chlamydia sp.The T cell response may include a CD4+ T cell response and / or a CD8+ T cell response, such as IFNγ-producing CD4+ T cells and / or IFNγ-producing CD8+ T cells. In some modalities, the T cell response includes CD4+ T cells, such as IFNγ-producing CD4+ T cells.

[00188] Protective immunity or protective immune response, as used herein, refers to immunity or the attainment of an immune response against an infectious agent (e.g., a Chlamydia pathogen) that is exhibited by an individual, which prevents or improves an infection or reduces at least one symptom thereof. Specifically, the induction of protective immunity or a protective immune response from the administration of a composition of the invention is evident by the elimination or reduction of the presence of one or more symptoms of chlamydia infection and / or an expansion of the population of chlamydia-responsive memory T cells. As used herein, the term immune response refers to both humoral and medial immune responses. Petition 870250077861, dated 01 / 09 / 2025, page 92 / 418 83 / 306 cell-mediated. Preferably, the protective immunity provided by the invention is characterized by protective immunological memory (e.g., a protective memory T cell response) against the pathogen. The protective immunity may be characterized by a population of pathogen-effective and responsive memory T cells (e.g., responsive to Chlamydia). In preferred embodiments, treatment with a composition of the invention, as described herein, provides protective immunity against reinfection by the Chlamydia pathogen. The protective immunity may be sterilizing immunity (i.e., complete protective immunity), whereby the protected individual can elicit an immune response that completely eliminates the infection. Chlamydia antigens described herein (e.g., the chimeric VD polypeptides of MOMP of the invention and the CT443 and CT584 polypeptides of Chlamydia sp. of the invention) may bind to Chlamydia sp. (e.g., C.trachomatis) elementary bodies, for example, elementary bodies of two or more serotypes. Nucleic acid compositions

[00189] In one aspect, the invention provides a composition comprising a nucleic acid as described herein, comprising a nucleotide sequence encoding a modified MOMP polypeptide as described herein.

[00190] In another aspect, the invention provides a composition comprising a nucleic acid as described herein, comprising a nucleotide sequence encoding a modified MOMP VD chimeric polypeptide as described herein.

[00191] In another aspect, the invention provides a composition comprising a nucleic acid as described in this document. Petition 870250077861, dated 01 / 09 / 2025, page 93 / 418 84 / 306 ment, which comprises a nucleotide sequence encoding a CT443 polypeptide from Chlamydia sp. as described herein.

[00192] In another aspect, the invention provides a composition comprising a nucleic acid as described herein, which comprises a nucleotide sequence encoding a CT584 polypeptide from Chlamydia sp. as described herein.

[00193] In another aspect, the invention provides a composition comprising a nucleic acid as described herein, which comprises a nucleotide sequence encoding a CT600 polypeptide from Chlamydia sp. as described herein.

[00194] In another aspect, the invention provides a composition comprising a nucleic acid as described herein, which comprises a nucleotide sequence encoding a CT812 polypeptide from Chlamydia sp. as described herein.

[00195] In a further aspect, the invention provides a composition comprising one, two, three or four of the following: (a) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a Chlamydia sp. CT443 polypeptide, as described herein; (b) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a Chlamydia sp. CT584 polypeptide, as described herein; (c) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a Chlamydia sp. CT600 polypeptide, as described herein; and / or (d) a nucleic acid, as described herein Petition 870250077861, dated 01 / 09 / 2025, page 94 / 418 85 / 306 document, which comprises a nucleotide sequence encoding a CT812 polypeptide from Chlamydia sp., as described in this document.

[00196] A composition of the invention may comprise a combination, as described herein, of the nucleic acids described herein (for example, they may be formulated in the same composition). The combinations described herein of the nucleic acids described herein may alternatively be in two or more separate compositions (for example, as a combination of compositions for simultaneous, separate or sequential administration (for example, in a therapeutic use as described herein)).

[00197] In some embodiments, the composition may comprise (a) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a modified MOMP polypeptide, as described herein, (b) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a chimeric VD polypeptide of MOMP, as described herein, and (c) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT443 polypeptide of Chlamydia sp., as described herein.

[00198] In some embodiments, the composition may comprise (a) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a modified MOMP polypeptide, as described herein, (b) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a poly Petition 870250077861, dated 01 / 09 / 2025, page 95 / 418 86 / 306 chimeric VD peptide of MOMP, as described herein, and (c) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT584 polypeptide of Chlamydia sp., as described herein.

[00199] Typically, the composition may comprise (a) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a modified MOMP polypeptide, as described herein, (b) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a chimeric VD polypeptide of MOMP, as described herein, (c) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT443 polypeptide of Chlamydia sp., as described herein, and (d) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT584 polypeptide of Chlamydia sp., as described herein.

[00200] A composition of the present description comprising one or more nucleic acids of the present description may also include one or more additional components, such as small molecule immunoenhancers (e.g., TLR agonists). A composition of the present description may also include a delivery system for a nucleic acid described herein (e.g., RNA), such as a liposome, an oil-in-water emulsion, or a microparticle. In some embodiments, the composition comprises a lipid nanoparticle (LNP). In certain embodiments, the composition comprises a nucleic acid molecule of the invention encapsulated within an LNP. Petition 870250077861, dated 01 / 09 / 2025, page 96 / 418 87 / 306 Polypeptide compositions

[00201] In one aspect, the invention provides a composition comprising a modified MOMP polypeptide, as described herein.

[00202] In another aspect, the invention provides a composition comprising a chimeric VD polypeptide of MOMP, as described in this document.

[00203] In another aspect, the invention provides a composition comprising a CT443 polypeptide from Chlamydia sp., as described in this document.

[00204] In another aspect, the invention provides a composition comprising a CT584 polypeptide from Chlamydia sp., as described in this document.

[00205] In another aspect, the invention provides a composition comprising a CT600 polypeptide from Chlamydia sp., as described in this document.

[00206] In another aspect, the invention provides a composition comprising a CT812 polypeptide from Chlamydia sp., as described in this document.

[00207] In a further aspect, the invention provides a composition comprising one, two, three or four of the following: (a) a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT443 polypeptide, as described herein; (b) a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT584 polypeptide, as described herein; (c) a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT600 polypeptide, as described herein; and / or (d) a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT812 polypeptide, as described herein. Petition 870250077861, dated 01 / 09 / 2025, page 97 / 418 88 / 306 document.

[00208] A composition of the invention may comprise a combination, as described herein, of the polypeptides described herein (for example, they may be formulated in the same composition). The combinations described herein of the polypeptides described herein may alternatively be in two or more separate compositions (for example, as a combination of compositions for simultaneous, separate or sequential administration (for example, in a therapeutic use as described herein)).

[00209] In some embodiments, the composition may comprise (i) a modified MOMP polypeptide as described herein, (ii) a chimeric VD polypeptide of MOMP as described herein, and (iii) a CT443 polypeptide of Chlamydia sp. as described herein.

[00210] In some embodiments, the composition may comprise (i) a modified MOMP polypeptide as described herein, (ii) a chimeric VD polypeptide of MOMP as described herein, and (iii) a CT584 polypeptide of Chlamydia sp. as described herein.

[00211] Typically, the composition may comprise (i) a modified MOMP polypeptide as described herein, (ii) a chimeric VD polypeptide of MOMP as described herein, (iii) a CT443 polypeptide from Chlamydia sp. as described herein, and (iv) a CT584 polypeptide from Chlamydia sp. as described herein.

[00212] A composition of the present description comprising one or more polypeptides of the present description may comprise an adjuvant. As used herein, an adjuvant refers to a substance or vehicle that enhances the response. Petition 870250077861, dated 01 / 09 / 2025, p. 98 / 418 89 / 306 immune to an antigen. Adjuvants may include, without limitation, a mineral suspension (e.g., alum, aluminum hydroxide, or phosphate) in which the antigen is adsorbed; a water-in-oil or oil-in-water emulsion in which the antigen solution is emulsified in mineral oil or water (e.g., Freund's incomplete adjuvant). Sometimes, killed mycobacteria are included (e.g., Freund's complete adjuvant) to further enhance antigenicity. Adjuvants may include squalene-based oil-in-water emulsion adjuvants (e.g., AF03, as described in document no. WO2007006939 and patent document no. US 8,703,095; AS03, as described in documents WO1995017209, WO1995017210 and patent documents no. US 6,623,739, 7,029,678 and 7,510,698; and MF59, as described in document no. WO1990014837 and patent documents no. US 6,299,884 and 6,451,325).Immunostimulatory oligonucleotides (e.g., CpG motif) can also be used as adjuvants (e.g., see U.S. Patents Nos. 6,194,388; 6,207,646; 6,214,806; 6,218,371; 6,239,116; 6,339,068; 6,406,705; and 6,429,199). Adjuvants may also include biological molecules such as Toll-Like receptor (TLR) agonists (e.g., AS01, as described in document no. WO2007068907 and patent documents no. US 10,039,823 and 10,143,745; SPA14, as described in document no. WO2022090359; and LEQ, as described in document no. WO2023056089) and co-stimulatory molecules. In some embodiments, the adjuvant is AF03 (an oil-in-water squalene-based emulsion adjuvant). In some embodiments, the adjuvant is one that can induce a Th1 response. Combinations of nucleic acids

[00213] The invention provides combinations comprising two Petition 870250077861, dated 01 / 09 / 2025, page 99 / 418 90 / 306 or more nucleic acids of the invention.

[00214] Thus, in one aspect, the invention provides a combination comprising a nucleic acid as described herein, comprising a nucleotide sequence encoding a modified MOMP polypeptide as described herein and: (i) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a chimeric VD polypeptide of MOMP, as described herein; and / or (ii) one or more of (a) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT443 polypeptide of Chlamydia sp., as described herein; (b) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT584 polypeptide from Chlamydia sp., as described herein; (c) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a Chlamydia sp. CT600 polypeptide, as described herein, and / or (d) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a Chlamydia sp. CT812 polypeptide, as described herein.

[00215] In some embodiments, the combination comprises the nucleic acid of (a), the nucleic acid of (b), the nucleic acid of (c), the nucleic acid of (d), the nucleic acids of (a) and (b), the nucleic acids Petition 870250077861, dated 01 / 09 / 2025, page 100 / 418 91 / 306 nucleic acids of (a) and (c), nucleic acids of (a) and (d), nucleic acids of (b) and (c), nucleic acids of (b) and (d), nucleic acids of (c) and (d), nucleic acids of (a), (b) and (c), nucleic acids of (a), (c) and (d), nucleic acids of (a), (b) and (d), nucleic acids of (b), (c) and (d), nucleic acids of (a), (b) and (d), nucleic acids of (b), (c) and (d) or nucleic acids of (a), (b), (c) and (d). In some embodiments, the combination comprises the nucleic acid of (a). In some embodiments, the combination comprises the nucleic acid of (b). Typically, the combination comprises the nucleic acid of (a) and the nucleic acid of (b).

[00216] The nucleic acids of any of (a)-(d) may be located in the same nucleic acid molecule. Alternatively, the nucleic acids of (a)-(d) may be separate nucleic acid molecules.

[00217] Thus, in some embodiments, a combination of the invention comprises a nucleic acid, as described herein, comprising a nucleotide sequence encoding a modified MOMP polypeptide, as described herein, and a nucleic acid, as described herein, comprising a nucleotide sequence encoding a chimeric VD polypeptide of MOMP, as described herein.

[00218] In some embodiments, a combination of the invention comprises a nucleic acid, as described herein, comprising a nucleotide sequence encoding a modified MOMP polypeptide, as described herein, and one, two, three or four of the following: (a) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT443 polypeptide from Chlamydia sp., as described herein; (b) a Petition 870250077861, dated 01 / 09 / 2025, p. 101 / 418 92 / 306 nucleic acid, as described herein, comprising a nucleotide sequence encoding a Chlamydia sp. CT584 polypeptide, as described herein; (c) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a Chlamydia sp. CT600 polypeptide, as described herein; and / or (d) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a Chlamydia sp. CT812 polypeptide, as described herein. The combination may comprise any of the non-MOMP antigen combinations (a)-(d) set forth above. In some embodiments, the combination comprises the nucleic acid of (a). In some embodiments, the combination comprises the nucleic acid of (b). Typically, the combination comprises the nucleic acid of (a) and the nucleic acid of (b).

[00219] In some embodiments, a combination of the invention comprises (i) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a modified MOMP polypeptide, as described herein; (ii) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a chimeric VD polypeptide of MOMP, as described herein; and (iii) one, two, three, or four of the nucleic acids in (a)-(d). The combination may comprise any of the non-MOMP antigen combinations (a)-(d) set forth above. In some embodiments, the combination comprises the nucleic acid of (a). In some embodiments, the combination comprises the nucleic acid of (b). Typically, the combination comprises the nucleic acid of (a) and the nucleic acid of (b).

[00220] In a further aspect, the invention provides a combi Petition 870250077861, dated 01 / 09 / 2025, page 102 / 418 93 / 306 nation comprising a nucleic acid as described herein, comprising a nucleotide sequence encoding a chimeric VD polypeptide of MOMP as described herein and one, two, three, or four of the nucleic acids in (a)-(d). The combination may comprise any of the non-MOMP antigen combinations (a)-(d) set forth above. In some embodiments, the combination comprises the nucleic acid of (a). In some embodiments, the combination comprises the nucleic acid of (b). Typically, the combination comprises the nucleic acid of (a) and the nucleic acid of (b). In some embodiments, the combination further comprises a nucleic acid, as described herein, comprising a nucleotide sequence encoding a modified MOMP polypeptide, as described herein.

[00221] In another aspect, the invention provides a combination comprising a nucleic acid, as described herein, comprising a nucleotide sequence encoding a Chlamydia sp. CT443 polypeptide, as described herein, and one, two or three of the nucleic acids as defined in (b)-(d). The combination may comprise any of the non-MOMP antigen combinations of (b), (c) and / or (d) set forth above. Typically, the combination comprises the nucleic acid of (b). In some embodiments, the combination further comprises a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. native MOMP polypeptide or a variant thereof.

[00222] In another aspect, the invention provides a combination comprising a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT584 polypeptide from Chlamydia sp., as described in Petition 870250077861, dated 01 / 09 / 2025, page 103 / 418 94 / 306 of this document, and one, two, or three of the nucleic acids as defined in (a), (c), or (d). The combination may comprise any of the non-MOMP antigen combinations from (a), (c), and / or (d) set forth above. Typically, the combination comprises the nucleic acid from (a). In some embodiments, the combination further comprises a nucleic acid comprising a nucleotide sequence encoding a native Chlamydia sp. MOMP polypeptide or a variant thereof.

[00223] In another aspect, the invention provides a combination comprising a nucleic acid, as described herein, comprising a nucleotide sequence encoding a Chlamydia sp. CT600 polypeptide, as described herein, and one, two or three of the nucleic acids as defined in (a), (b) or (d). The combination may comprise any of the non-MOMP antigen combinations of (a), (b) and / or (d) set forth above. In some embodiments, the combination further comprises a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. native MOMP polypeptide or a variant thereof.

[00224] In another aspect, the invention provides a combination comprising a nucleic acid, as described herein, comprising a nucleotide sequence encoding a Chlamydia sp. CT812 polypeptide, as described herein, and one, two or three of the nucleic acids as defined in (a)-(c). The combination may comprise any of the non-MOMP antigen combinations of (a), (b) and / or (c) set forth above. In some embodiments, the combination further comprises a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. native MOMP polypeptide or a variant thereof. Petition 870250077861, dated 01 / 09 / 2025, page 104 / 418 95 / 306

[00225] Thus, the combination of the invention may comprise a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. native MOMP polypeptide or a variant thereof, and one, two, three or four of the nucleic acids in (a)-(d). Variants of a Chlamydia sp. native MOMP polypeptide include MOMP polypeptides comprising one or more conservative amino acid substitutions, MOMP polypeptides comprising a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in a Chlamydia sp. native MOMP polypeptide, and MOMP polypeptides comprising a single amino acid substitution at one or more (e.g., all) positions corresponding to a glycosylation site, preferably an N-glycosylation site, in a Chlamydia sp. native MOMP polypeptide.They also include MOMP polypeptides comprising a secretion signal peptide sequence and MOMP polypeptides comprising a heterologous transmembrane domain. In some embodiments, a variant of a Chlamydia sp. native MOMP polypeptide comprises a secretion signal peptide sequence. In some embodiments, a variant of a Chlamydia sp. native MOMP polypeptide comprises a secretion signal peptide sequence and a heterologous transmembrane domain.

[00226] The nucleic acid combinations disclosed herein encompass all individual nucleic acids being in the same composition and all individual nucleic acids being in one or more separate compositions. In some embodiments, all individual nucleic acids in a combination as described herein are in the same composition. In some embodiments, each of the nucleic acids in a combination Petition 870250077861, dated 01 / 09 / 2025, page 105 / 418 96 / 306 The combination as described herein is a separate composition. In some embodiments, two or more nucleic acids in a combination as described herein are in two or more compositions. In some embodiments of the combinations of the invention, one, two, three, or four of the nucleic acids from (a)(d) above are in one or more compositions. In some embodiments of the combinations of the invention, the two, three, or four nucleic acids from (a)-(d) above are in two or more separate compositions. Typically, all individual nucleic acids are in the same composition. Polypeptide combinations

[00227] The invention provides combinations comprising two or more polypeptides of the invention.

[00228] Thus, in one aspect, the invention provides a combination comprising a modified MOMP polypeptide, as described herein, and: (i) a chimeric VD DE MOMP polypeptide as described herein; and / or (ii) one or more of (a) a polypeptide comprising an amino acid sequence of a CT443 polypeptide from Chlamydia sp., as described herein; (b) a polypeptide comprising an amino acid sequence of a CT584 polypeptide from Chlamydia sp., as described herein; (c) a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT600 polypeptide, as described herein and / or (d) a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT812 polypeptide, as described herein Petition 870250077861, dated 01 / 09 / 2025, page 106 / 418 97 / 306 described in this document.

[00229] In some embodiments, the combination comprises the polypeptide of (a), the polypeptide of (b), the polypeptide of (c), the polypeptide of (d), the polypeptides of (a) and (b), the polypeptides of (a) and (c), the polypeptides of (a) and (d), the polypeptides of (b) and (c), the polypeptides of (b) and (d), the polypeptides of (c) and (d), the polypeptides of (a), (b) and (c), the polypeptides of (a), (c) and (d), the polypeptides of (a), (b) and (d), the polypeptides of (b), (c) and (d), the polypeptides of (a), (b), (c) and (d). In some embodiments, the combination comprises the polypeptide of (a). In some embodiments, the combination comprises the polypeptide of (b). Typically, the combination comprises the polypeptide of (a) and the polypeptide of (b).

[00230] Thus, in some embodiments, a combination of the invention comprises a modified MOMP polypeptide, as described herein, and a chimeric VD polypeptide of MOMP, as described herein.

[00231] In some embodiments, a combination of the invention comprises a modified MOMP polypeptide, as described herein, and one, two, three, or four of the following: (a) a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT443 polypeptide, as described herein; (b) a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT584 polypeptide, as described herein; (c) a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT600 polypeptide, as described herein; and / or (d) a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT812 polypeptide, as described herein. The combination may comprise any of the non-MOMP antigen combinations (a)-(d) set forth above. In Petition 870250077861, dated 01 / 09 / 2025, page 107 / 418 98 / 306 In some embodiments, the combination comprises the polypeptide of (a). In some embodiments, the combination comprises the polypeptide of (b). Typically, the combination comprises the polypeptide of (a) and the polypeptide of (b).

[00232] In some embodiments, a combination of the invention comprises (i) a modified MOMP polypeptide, as described herein; (ii) a chimeric VD MOMP polypeptide, as described herein; and (iii) one, two, three, or four of the polypeptides in (a)-(d). The combination may comprise any of the non-MOMP antigen combinations (a)-(d) set forth above. In some embodiments, the combination comprises the polypeptide of (a). In some embodiments, the combination comprises the polypeptide of (b). Typically, the combination comprises the polypeptide of (a) and the polypeptide of (b).

[00233] In a further aspect, the invention provides a combination comprising a chimeric VD MOMP polypeptide, as described herein, and one, two, three, or four of the polypeptides in (a)-(d). The combination may comprise any of the non-MOMP antigen combinations (a)-(d) set forth above. In some embodiments, the combination comprises the polypeptide of (a). In some embodiments, the combination comprises the polypeptide of (b). Typically, the combination comprises the polypeptide of (a) and the polypeptide of (b). In some embodiments, the composition further comprises a modified MOMP polypeptide, as described herein.

[00234] In another aspect, the invention provides a combination comprising a polypeptide comprising an amino acid sequence of a CT443 polypeptide from Chlamydia sp., as described herein, and one, two or three of the polypeptides as defined in (b)-(d). The combination may comprise which Petition 870250077861, dated 01 / 09 / 2025, page 108 / 418 99 / 306 requires one of the non-MOMP antigen combinations from (b), (c), and / or (d) set forth above. Typically, the combination comprises the polypeptide from (b). In some embodiments, the combination further comprises a native Chlamydia sp. MOMP polypeptide or a variant thereof.

[00235] In another aspect, the invention provides a combination comprising a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT584 polypeptide, as described herein, and one, two or three of the polypeptides as defined in (a), (c) or (d). The combination may comprise any of the non-MOMP antigen combinations of (a), (c) and / or (d) set forth above. Typically, the combination comprises the polypeptide of (a). In some embodiments, the combination further comprises a native Chlamydia sp. MOMP polypeptide or a variant thereof.

[00236] In another aspect, the invention provides a combination comprising a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT600 polypeptide, as described herein, and one, two or three of the polypeptides as defined in (a), (b) or (d). The combination may comprise any of the non-MOMP antigen combinations of (a), (b) and / or (d) set forth above. In some embodiments, the combination further comprises a native Chlamydia sp. MOMP polypeptide or a variant thereof.

[00237] In another aspect, the invention provides a combination comprising a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT812 polypeptide, as described herein, and one, two or three of the polypeptides as defined in (a)-(c). The combination may comprise any of the non-MOMP antigen combinations of (a), (b) and / or Petition 870250077861, dated 01 / 09 / 2025, page 109 / 418 100 / 306 (c) established above. In some embodiments, the combination further comprises a native Chlamydia sp. MOMP polypeptide or a variant thereof.

[00238] Thus, a combination of the invention may comprise a native Chlamydia sp. MOMP polypeptide or a variant thereof and one, two, three or four of the polypeptides in (a)-(d). Variants of a native Chlamydia sp. MOMP polypeptide include MOMP polypeptides comprising one or more conservative amino acid substitutions, MOMP polypeptides comprising a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in a native Chlamydia sp. MOMP polypeptide, and MOMP polypeptides comprising a single amino acid substitution at one or more (e.g., all) positions corresponding to a glycosylation site, preferably an N-glycosylation site, in a native Chlamydia sp. MOMP polypeptide.They also include MOMP polypeptides comprising a secretion signal peptide sequence and MOMP polypeptides comprising a heterologous transmembrane domain. In some embodiments, a variant of a Chlamydia sp. native MOMP polypeptide comprises a secretion signal peptide sequence. In some embodiments, a variant of a Chlamydia sp. native MOMP polypeptide comprises a secretion signal peptide sequence and a heterologous transmembrane domain.

[00239] The polypeptide combinations disclosed herein encompass all individual polypeptides in the same composition and all individual polypeptides in one or more separate compositions. In some embodiments, all individual polypeptides in a combination described herein are present. Petition 870250077861, dated 01 / 09 / 2025, page 110 / 418 101 / 306 see document are in the same composition. In some embodiments, each of the polypeptides in a combination as described herein is in a separate composition. In some embodiments, two or more polypeptides in a combination as described herein are in two or more compositions. In some embodiments of the combinations of the invention, one, two, three or four of the polypeptides from (a)-(d) above are in one or more compositions. In some embodiments of the combinations of the invention, the two, three or four polypeptides from (a)(d) above are in two or more separate compositions. Typically, all individual polypeptides are in the same composition. LNPs

[00240] In certain embodiments, the composition of the invention (for example, the composition comprising a nucleic acid of the invention) further comprises a lipid nanoparticle (LNP). In certain embodiments, the nucleic acid of the invention is encapsulated within the LNP.

[00241] The LNPs described may comprise four categories of lipids: (i) an ionizable lipid (e.g., cationic lipid); (ii) a PEGylated lipid; (iii) a cholesterol-based lipid; and (iv) an auxiliary lipid. A. Ionizable Lipids

[00242] An ionizable lipid facilitates mRNA encapsulation and can be a cationic lipid. A cationic lipid provides a positively charged environment at low pH to facilitate efficient encapsulation of the negatively charged mRNA drug substance.

[00243] In some embodiments, the cationic lipid is OF-02: Petition 870250077861, dated 01 / 09 / 2025, page 111 / 418 102 / 306

[00244] OF-02 is a non-degradable structural analog of OF-DegLin. OF-Deg-Lin contains degradable ester linkages to attach the diketopiperazine core and the doubly unsaturated tails, while OF-02 contains non-degradable 1,2-aminoalcohol linkages to attach the same diketopiperazine core and the doubly unsaturated tails (Fenton et al., Adv Mater. (2016) 28:2939; US patent document no. 10,201,618). An exemplary LNP formulation in the present document, Lipid A, contains OF-02.

[00245] In some embodiments, the cationic lipid is cKK-E10 (Dong et al., PNAS (2014) 111(11):3955-60; US patent document no. 9,512,073): Petition 870250077861, dated 01 / 09 / 2025, p. 112 / 418 103 / 306 CKK-E10 Formula (II)

[00246] An exemplary LNP formulation in this document, Lipid B, contains cKK-E10.

[00247] In some embodiments, the cationic lipid is GL-HEPESE3-E10-DS-3-E18-1 4-(bis(2-hydroxydecyl)amino)butanoate) of (2-(4-(2((3-(Bis((Z)-2-hydroxyoctadec-9-en-1yl)amino)propyl)disulfaneyl)ethyl)piperazin-1-yl)ethyl, which is a HEPES-based disulfide cationic lipid with a piperazine core, which has Formula III: Formula (III)

[00248] An exemplary LNP formulation in this document, Lipid C, contains GL-HEPES-E3-E10-DS-3-E18-1. Lipid C has the same composition as Lipid A or Lipid B, but is different from the cationic lipid.

[00249] In some embodiments, the cationic lipid is GL-HEPES Petition 870250077861, dated 01 / 09 / 2025, page 113 / 418 104 / 306 E3-E12-DS-4-E10 4-(bis(2-hydroxydodecyl)amino)butanoate) of (2-(4(2-((3-(bis(2-hydroxydecyl)amino)butyl)disulfaneyl)ethyl)piperazin-1-yl)ethyl), which is a HEPES-based disulfide cationic lipid with a piperazine core, which has Formula IV:

[00250] An exemplary LNP formulation in this document, Lipid D, contains GL-HEPES-E3-E12-DS-4-E10. Lipid D has the same composition as Lipid A or Lipid B, but is different from the cationic lipid.

[00251] In some embodiments, the cationic lipid is GL-HEPESE3-E12-DS-3-E14 4-(bis(2-hydroxydodecyl)amino)butanoate) of (2-(4(2-((3-(Bis(2-hydroxytetradecyl)amino)propyl)disulfaneyl)ethyl)piperazin-1-yl)ethyl), which is a HEPES-based disulfide cationic lipid with a piperazine core, which has Formula V: Petition 870250077861, dated 01 / 09 / 2025, page 114 / 418 105 / 306

[00252] An exemplary LNP formulation in this document, Lipid E, contains GL-HEPES-E3-E12-DS-3-E14. Lipid E ​​has the same composition as Lipid A or Lipid B, but is different from the cationic lipid.

[00253] The cationic lipids GL-HEPES-E3-E10-DS-3-E18-1 (III), GL-HEPES-E3-E12-DS-4-E10 (IV) and GL-HEPES-E3-E12-DS-3-E14 (V) can be synthesized according to the general procedure established in Scheme 1: Scheme 1; General Synthetic Scheme for Lipids of Formulas (III), (IV) and (V)

[00254] In some forms, the cationic lipid is MC3, which has Formula VI: Petition 870250077861, dated 01 / 09 / 2025, page 115 / 418 106 / 306 Formula (VI)

[00255] In some embodiments, the cationic lipid is SM-102 (9-heptadecanyl 8-(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]aminooctanoate), which has Formula VII: Formula (VII)

[00256] In some embodiments, the cationic lipid is ALC-0315 [(4-hydroxybutyl)azanedi-yl]di(hexane-6,1-di-yl)bis(2-hexyldecanoate), which has Formula VIII:

[00257] In some embodiments, the cationic lipid is cOrn-EE1 which has Formula IX: the the Formula (IX)

[00258] In some embodiments, the cationic lipid is ATX-126 (4,4'-[[[[3-(dimethylamino)propyl]thio]carbonyl]imino]b / s-butanoic acid, 1,1'-bis(1-heptiloctyl) ester), which has the formula X: Petition 870250077861, dated 01 / 09 / 2025, p. 116 / 418 107 / 306

[00259] In some embodiments, the cationic lipid may be selected from the group comprising cKK-E10; OF-02; [(6Z,9Z,28Z,31Z)heptatriaconta-6,9,28,31-tetraen-19-yl] 4-(dimethylamino)butanoate (DLin-MC3-DMA); 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLinKC2-DMA); 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (Dlin-DMA); di((Z)-non-2-en-1-yl) 9-((4(dimethylamino)butanoyl)oxy)heptadecanedioate (L319); 9-heptadecanyl 8-{(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino}octanoate (SM-102); [(4-hydroxybutyl)azanediyl]di(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC-0315); [3-(dimethylamino)-2-[(Z)-octadec-9-enoyl]oxypropyl] (Z)octadec-9-enoate (DODAP); 2,5-bis(3-aminopropylamino)-N-[2[di(heptadecyl)amino]-2-oxoethyl]pentanamide (DOGS); [(3S,8S,9S, 10R, 13R, 14S, 17R)-10,13-d imet yl-17-[(2R)-6-methylheptane-2yl]-2,3,4,7,8,9,11,12,14,15,16,17-hydrododeca-17-dodeca Hcyclopenta[a]phenanthren-3-yl] N-[2-(dimethylamino)ethyl]carbamate (DCChol); tetraquis(8-methylnonyl) 3,3',3,3'-(((methylazanedyl) bis(propano3,1 diyl))bis(azanetriyl))tetrapropionate (3060Í10); decyl (2(dioctylammonium)ethyl) phosphate (9A1P9); 5,5-di((Z)-heptadec-8-en-1-yl)-1(3-(pyrrolidin-1 -yl)propyl)-2,5-di-hydro-1 H-imidazole-2-ethyl carboxylate (A2-lso5-2DC18); 3,3'-((3-methyl-9-oxo-10-oxa-13,14-d itia-3,6diazahexacosyl)azanediyl)dipropionate of bis(2Petição 870250077861, of 01 / 09 / 2025, p. 117 / 41818). 108 / 306 (dodecyldisulfanyl)ethyl)azanediyl)dipropionate (BAME-O16B); 1,1 -((2-(4(2-((2-(bis(2-hidroxidodecyl)amino)ethyla) (2-hidroxidodecyl)amino)ethyla) piperazin-1 -yl)ethyl)azanediyl) bis(dodecan-2-ol) (C12-200); 3,6-bis(4(bis(2-hidroxidodecyl)amino)butyl)piperazine-2,5-diona (CKK-E12); hexa(octan-3-yl) 9,9',9,9',9,9'- ((((benzeno-1,3,5tricarbonyl)iris(azanediyl)) tris(propane-3,1 -dii la)) tris(azanetriyl))hexanonanoate (FTT5); (((3,6-dioxopiperazine-2,5-diyl)bis(butane-4, 1 -di-yl))bis(azanetri-yl))tetraquis(ethane-2,1 -di-yl) (9Z,9'Z,9Z,9'Z, 12Z, 12'Z, 12Z, 12'Z)-tetraquis(octadeca-9,12-dienoate) (OF-Deg-Lin); TT3; N1, N3, N5-tris(3-(didodecylamino)propyl)benzeno1,3,5-tricarboxamida; N1-[2-((1S)-1-[(3-aminopropyl)amino]-4-[di(3aminopropyl)amino]butylcarboxamido)ethyl]-3,4-di[oleylóxi]-benzamida (MVL5); heptadecan-9-yl 8-((2-hidroxyethyl)(8-(nonylóxi)-8oxooctyl)amino)octanoate (Lipid 5);4,4'-[[[[3(dimethylamino)propyl]thio]carbonyl]imino]bis-butanoic acid, 1,1'-bis(1-heptiloctyl) ester (ATX-126) GL-HEPES-E3-E10-DS-3-E18-1; GL-HEPES-E3-E12-DS-4-E10; GL-HEPES-E3-E12-DS-3-E14, IM-001 and combinations thereof.;

[00260] In some embodiments, the cationic lipid is IM-001, with

[00261] An exemplary LNP formulation in this document, Lipid G, contains IM-001. Lipid G has the same composition as Lipid A or Lipid B, but is different from the cationic lipid.

[00262] The cationic lipid IM-001 (XI) can be synthesized according to the general procedure established in Scheme 2: Petition 870250077861, dated 01 / 09 / 2025, page 118 / 418 109 / 306 Scheme 2: General Synthetic Scheme for Lipid of Formula (XI) OTBS TBSO''*''-^^ 2 HFPy THE IM-001

[00263] Scheme 2 can be executed as described in Example 14.

[00264] In some embodiments, the cationic lipid is biodegradable.

[00265] In some embodiments, the cationic lipid is not biodegradable.

[00266] In some embodiments, the cationic lipid is cleavable.

[00267] In some embodiments, the cationic lipid is not cleavable.

[00268] Cationic lipids are described in further detail in Dong et al. (PNAS. 111(11):3955-60. 2014); Fenton et al. (Adv Mater. 28:2939. 2016); U.S. Patent No. 9,512,073 and U.S. Patent No. 10,201,618, each of which is incorporated herein in its entirety by reference. B. PEGylated Lipids

[00269] The PEGylated lipid component provides control over particle size and nanoparticle stability. The addition of such components can prevent complex aggregation and provides a means to increase circulation lifetime and enhance delivery of the nucleic acid-lipid pharmaceutical composition to target tissues (Klibanov et al. FEBS Letters 268 (1): 235-7. 1990). These components can be selected to rapidly change the pharmaceutical composition in vivo (see, for example, US patent document no. 5,885,613). Petition 870250077861, dated 01 / 09 / 2025, page 119 / 418 110 / 306

[00270] The PEGylated lipids contemplated include, but are not limited to, a polyethylene glycol (PEG) chain up to 5 kDa in length covalently attached to a lipid with an alkyl chain (or chains) of C6-C20 length (e.g., C8, C10, C12, C14, C16 or C18), such as a ceramide derivative (e.g., N-octanoyl-sphingosine-1-[succinyl(methoxypolyethylene glycol)] (C8 PEG ceramide)). In some embodiments, the PEGylated lipid is 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol (DMG-PEG); 1,2-diestearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol (DSPE-PEG); 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol (DLPEPEG); or 1,2-diestearoyl-rac-glycero-polyethylene glycol (DSG-PEG), PEGDAG; PEG-PE; PEG-S-DAG; PEG-S-DMG; PEG-cer; a PEG dialkyloxypropylcarbamate; 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159) and combinations thereof.

[00271] In certain embodiments, PEG has a high molecular weight, for example, 2000-2400 g / mol. In certain embodiments, PEG is PEG2000 (or PEG-2K). In certain embodiments, the PEGylated lipid in this document is DMG-PEG2000, DSPE-PEG2000, DLPE-PEG2000, DSG-PEG2000, C8 PEG2000 or ALC-0159 (2[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide). In certain embodiments, the PEGylated lipid in this document is DMG-PEG2000. C. Cholesterol-Based Lipids

[00272] The cholesterol component provides stability to the lipid bilayer structure within the nanoparticle. In some embodiments, LNPs comprise one or more cholesterol-based lipids. Suitable cholesterol-based lipids include, for example: DC-Choi (N,N-dimethyl-N-ethylcarboxamidocholesterol), l,4-bis(3-Noleylaminopropyl)piperazine (Gao et al., Biochem Biophys Res Comm. (1991) 179:280; Wolf et al., BioTechniques (1997) 23:139; US patent document no. 5,744,335), imidazole cholesterol ester (ICE; do Petition 870250077861, dated 01 / 09 / 2025, page 120 / 418 111 / 306 document no. WO2011 / 068810), sitosterol (22,23-dihydrostigmasterol), β-sitosterol, sitostanol, fucosterol, stigmasterol (stigmasta-5,22-dien3-ol), ergosterol; desmosterol (3B-hydroxy-5,24-cholestadiene); lanosterol (8,24-lanostadien-3b-ol); 7-dehydrocholesterol ^5,7-cholesterol); dihydrolanosterol (24,25-dihydrolanosterol); zymosterol (5a-cholesta-8,24dien-3B-ol); lathosterol (5a-cholesto-7-en-3B-ol); diosgenin ((3e,25R)spirost-5-en-3-ol); Campesterol (campest-5-en-3B-ol); campestanol (5a-campestan-3b-ol); 24-methylene cholesterol (5,24(28)-cholestadien-24methylene-3B-ol); cholesteryl margarine (cholest-5en-3B-yl heptadecanoate); cholesteryl oleate; cholesteryl stearate and other modified forms of cholesterol. In some embodiments, the cholesterol-based lipid used in LNPs is cholesterol. D. Auxiliary Lipids

[00273] An auxiliary lipid enhances the structural stability of the LNP and helps the LNP escape from the endosome. This improves the uptake and release of the drug payload from mRNA. In some embodiments, the auxiliary lipid is a zwitterionic lipid, which has fusogenic properties to enhance the uptake and release of the drug payload. Examples of auxiliary lipids are 1,2-dioleoyl-SN-glycero-3-phosphoethanolamine (DOPE); 1,2-diestearoyl-SN-glycero-3-phosphocholine (DSPC); 1,2-dioleoyl-SN-glycero-3-phospho-L-serine (DOPS); 1,2-dielaidoylsn-glycero-3-phosphoethanolamine (DEPE); and 1,2-dioleoyl-sn-glycero-3phosphocholine (DPOC), dipalmitoylphosphatidylcholine (DPPC), DMPC, 1,2dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2Distearoylphosphatidylethanolamine (DSPE) and 1,2-dilauroyl-sn-glycero-3phosphoethanolamine (DLPE).

[00274] Other illustrative auxiliary lipids are dileoylphosphatidylcholine (DOPC), dileoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), palmitoylleoylphosphatidylcholine (POPC), palmitoylleoylphosphatidylethanolamine (POPE), dileoyl-phosphatidylethanolamine 4-(N Petition 870250077861, dated 01 / 09 / 2025, page 121 / 418 112 / 306 maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), dipalmitoyl phosphatidyl ethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), phosphatidylserine, sphingolipids, sphingomyelins, ceramides, cerebrosides, gangliosides, 16-O-monomethyl PE, 16-O-dimethyl PE, 18-1-trans PE, lestearoyl-2-oleoyl-phosphatidiethanolamine (SOPE) or a combination thereof. In certain embodiments, the auxiliary lipid is DOPE. In certain embodiments, the auxiliary lipid is DSPC.

[00275] In various embodiments, the present LNPs comprise (i) a cationic lipid selected from OF-02, cKK-E10, GL-HEPESE3-E10-DS-3-E18-1, GL-HEPES-E3-E12-DS-4-E10, GL-HEPES-E3E12-DS-3-E14 or IM-001; (ii) DMG-PEG2000; (iii) cholesterol and (iv) DOPE.

[00276] In other forms, the present LNPs comprise (i) SM-102; (ii) DMG-PEG2000; (iii) cholesterol and (iv) DSPC.

[00277] In still other forms, the present LNPs comprise (i) ALC-0315; (ii) ALC-0159; (iii) cholesterol and (iv) DSPC.

[00278] In still other forms, the present LNPs comprise (i) ATX-126, (ii) DMG-PEG2000, (iii) cholesterol and (iv) DSPC. E. Molar Ratios of Lipid Components

[00279] The molar ratios of the above components are important for the effectiveness of LNPs in mRNA delivery. The molar ratio of the cationic lipid, PEGylated lipid, cholesterol-based lipid, and auxiliary lipid is A:B:C:D, where A + B + C + D = 100%. In some embodiments, the molar ratio of the cationic lipid in LNPs relative to the total lipids (i.e., A) is 35-55%, as 35-50% (e.g., 38-42%, as 40%, or 45-50%). In some embodiments, the molar ratio of the PEGylated lipid component relative to the total lipids (i.e., B) is 0.25-2.75% (e.g., 1-2%, as 1.5%). In some forms, the molar ratio of cholesterol-based lipid to total lipids (i.e., C) is 20-50% (for example) Petition 870250077861, dated 01 / 09 / 2025, page 122 / 418 113 / 306 plo, 27-30%, such as 28.5% or 38-43%). In some embodiments, the molar ratio of the auxiliary lipid to the total lipids (i.e., D) is 5-35% (e.g., 28-32%, such as 30%, or 8-12%, such as 10%). In some embodiments, the components (PEGylated lipid + cholesterol) have the same molar quantity as the auxiliary lipid. In some embodiments, LNPs contain a molar ratio between the cationic lipid and the auxiliary lipid that is greater than 1.

[00280] In certain embodiments, the LNP of the description comprises: a cationic lipid in a molar ratio of 35% to 55% or 40% to 50% (for example, a cationic lipid in a molar ratio of 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54% or 55%); a lipid conjugated with polyethylene glycol (PEG) (PEGylated) in a molar ratio of 0.25% to 2.75% or 1.00% to 2.00% (for example, a PEGylated lipid in a molar ratio of 0.25%, 0.50%, 0.75%, 1.00%, 1.25%, 1.50%, 1.75%, 2.00%, 2.25%, 2.50% or 2.75%); a cholesterol-based lipid in a molar ratio of 20% to 50%, 25% to 45% or 28.5% to 43% (for example, a cholesterol-based lipid in a molar ratio of 20%, 21%, 22%, 23%, 24%, 25%, %, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, %, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, %, 49% or 50%); and an auxiliary lipid in a molar ratio of 5% to 35%, 8% to 30%, or 10% to 30% (for example, an auxiliary lipid in a molar ratio of 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, or 35%), where all molar ratios are in with respect to the total lipid content of LNP.

[00281] In certain forms, LNP comprises: a lipid ca Petition 870250077861, dated 01 / 09 / 2025, p. 123 / 418 114 / 306 thionic acid in a molar ratio of 40%; a PEGylated lipid in a molar ratio of 1.5%; a cholesterol-based lipid in a molar ratio of 28.5%; and an auxiliary lipid in a molar ratio of 30%.

[00282] In certain embodiments, LNP comprises: a cationic lipid in a molar ratio of 45 to 50%; a PEGylated lipid in a molar ratio of 1.5 to 1.7%; a cholesterol-based lipid in a molar ratio of 38 to 43%; and an auxiliary lipid in a molar ratio of 9 to 10%.

[00283] In certain embodiments, the PEGylated lipid is dimyristoylPEG2000 (DMG-PEG2000).

[00284] In several forms, the cholesterol-based lipid is cholesterol.

[00285] In some embodiments, the auxiliary lipid is 1,2-dioleoylSN-glycero-3-phosphoethanolamine (DOPE).

[00286] In certain embodiments, LNP comprises: OF-O2 in a molar ratio of 35% to 55%; DMG-PEG2000 in a molar ratio of 0.25% to 2.75%; cholesterol in a molar ratio of 20% to 50% and DOPE in a molar ratio of 5% to 35%.

[00287] In certain embodiments, LNP comprises: cKK-E10 in a molar ratio of 35% to 55%; DMG-PEG2000 in a molar ratio of 0.25% to 2.75%; cholesterol in a molar ratio of 20% to 50% and DOPE in a molar ratio of 5% to 35%.

[00288] In certain embodiments, LNP comprises: GL-HEPESE3-E10-DS-3-E18-1 in a molar ratio of 35% to 55%; DMGPEG2000 in a molar ratio of 0.25% to 2.75%; cholesterol in a molar ratio of 20% to 50% and DOPE in a molar ratio of 5% to 35%.

[00289] In certain embodiments, LNP comprises: GL-HEPESE3-E12-DS-4-E10 in a molar ratio of 35% to 55%; DMGPEG2000 in a molar ratio of 0.25% to 2.75%; cholesterol in a Petition 870250077861, dated 01 / 09 / 2025, page 124 / 418 115 / 306 molar ratio of 20% to 50% and DOPE in a molar ratio of 5% to 35%.

[00290] In certain embodiments, LNP comprises: GL-HEPESE3-E12-DS-3-E14 in a molar ratio of 35% to 55%; DMGPEG2000 in a molar ratio of 0.25% to 2.75%; cholesterol in a molar ratio of 20% to 50% and DOPE in a molar ratio of 5% to 35%.

[00291] In certain embodiments, LNP comprises: SM-102 in a molar ratio of 35% to 55%; DMG-PEG2000 in a molar ratio of 0.25% to 2.75%; cholesterol in a molar ratio of 20% to 50%; and DSPC in a molar ratio of 5% to 35%.

[00292] In certain embodiments, LNP comprises: ALC-0315 in a molar ratio of 35% to 55%; ALC-0159 in a molar ratio of 0.25% to 2.75%; cholesterol in a molar ratio of 20% to 50% and DSPC in a molar ratio of 5% to 35%.

[00293] In certain embodiments, LNP comprises: OF-O2 in a molar ratio of 40%; DMG-PEG2000 in a molar ratio of 1.5%; cholesterol in a molar ratio of 28.5% and DOPE in a molar ratio of 30%. This LNP formulation is designated Lipid A in this document.

[00294] In certain embodiments, LNP comprises: cKK-E10 in a molar ratio of 40%; DMG-PEG2000 in a molar ratio of 1.5%; cholesterol in a molar ratio of 28.5% and DOPE in a molar ratio of 30%. This LNP formulation is designated Lipid B in this document.

[00295] In certain embodiments, LNP comprises: GL-HEPESE3-E10-DS-3-E18-1 in a molar ratio of 40%; DMG-PEG2000 in a molar ratio of 1.5%; cholesterol in a molar ratio of 28.5% and DOPE in a molar ratio of 30%. This LNP formulation is designated Lipid C in this document. Petition 870250077861, dated 01 / 09 / 2025, page 125 / 418 116 / 306

[00296] In certain embodiments, LNP comprises: GL-HEPESE3-E12-DS-4-E10 in a molar ratio of 40%; DMG-PEG2000 in a molar ratio of 1.5%; cholesterol in a molar ratio of 28.5% and DOPE in a molar ratio of 30%. This LNP formulation is designated Lipid D in this document.

[00297] In certain embodiments, LNP comprises: GL-HEPESE3-E12-DS-3-E14 in a molar ratio of 40%; DMG-PEG2000 in a molar ratio of 1.5%; cholesterol in a molar ratio of 28.5% and DOPE in a molar ratio of 30%. This LNP formulation is designated Lipid E ​​in this document.

[00298] In certain embodiments, LNP comprises: DLin-MC3DMA (MC3) in a molar ratio of 50%; DMG-PEG2000 in a molar ratio of 1.5%; cholesterol in a molar ratio of 38.5% and DSPC in a molar ratio of 10%. This LNP formulation is designated Lipid F in this document.

[00299] In certain embodiments, LNP comprises: IM-001 at a molar ratio of 40%; DMG-PEG2000 at a molar ratio of 1.5%; cholesterol at a molar ratio of 28.5% and DOPE at a molar ratio of 30%. This LNP formulation is designated Lipid G in this document.

[00300] In certain embodiments, LNP comprises: 8-{(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino}octanoate of 9-heptadecanyl (SM-102) in a molar ratio of 50%; 1,2-diestearoylsn-glycero-3-phosphocholine (DSPC) in a molar ratio of 10%; cholesterol in a molar ratio of 38.5%; and 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (DMG-PEG2000) in a molar ratio of 1.5%.

[00301] In certain embodiments, LNP comprises: [(4-Hydroxybutyl)azanodi-yl]di(hexane-6,1-di-yl)bis(2-hexyldecanoate) (ALC0315) in a molar ratio of 46.3%; 1,2-diestearoyl-sn-glycero-3-Petition 870250077861, dated 01 / 09 / 2025, page 126 / 418 117 / 306 phosphocholine (DSPC) in a molar ratio of 9.4%; cholesterol in a molar ratio of 42.7% and 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159) in a molar ratio of 1.6%.

[00302] In certain embodiments, LNP comprises: [(4-hydroxybutyl)azanodi-yl]di(hexane-6,1-di-yl)bis(2-hexyldecanoate) (ALC0315) in a molar ratio of 47.4%; 1,2-diestearoyl-sn-glycero-3-phosphocholine (DSPC) in a molar ratio of 10%; cholesterol in a molar ratio of 40.9%; and 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159) in a molar ratio of 1.7%.

[00303] In certain embodiments, LNP comprises 4,4'-[[[[3(dimethylamino)propyl]thio]carbonyl]imino]bis-butanoic acid, 1,1-bis(1-heptiloctyl) ester (ATX-126) in a molar ratio of 50%; DMGPEG2000 in a molar ratio of 1.5%; cholesterol in a molar ratio of 38.5%; and DSPC in a molar ratio of 10%.

[00304] In some embodiments, the LNP formulation is as defined for Lipid A, Lipid B, Lipid D, or Lipid G (e.g., Lipid D or Lipid G).

[00305] In order to calculate the actual amount of each lipid to be placed in an LNP formulation, the molar quantity of the cationic lipid is first determined based on a desired N / P ratio, where N is the number of nitrogen atoms in the cationic lipid, and P is the number of phosphate groups in the mRNA to be carried by the LNP. Then, the molar quantity of each of the other lipids is calculated based on the molar quantity of the cationic lipid and the selected molar ratio. The molar quantities are then converted using the molecular weight of each lipid. F. Nucleic acids in LNPs

[00306] The LNP compositions described herein may comprise a nucleic acid (e.g., mRNA) of the present invention. Petition 870250077861, dated 01 / 09 / 2025, p. 127 / 418 118 / 306

[00307] When desired, the LNP can be multivalent. In some embodiments, the LNP can carry nucleic acids, such as mRNAs, that encode more than one polypeptide of the present invention, such as two, three, four, five, six, seven, or eight polypeptides. For example, the LNP can carry multiple nucleic acids of the present invention (e.g., mRNA), each encoding a different polypeptide of the invention, or carry a polycistronic mRNA that can be translated into more than one polypeptide of the invention (e.g., each antigen-coding sequence is separated by a nucleotide linker encoding a self-cleavable peptide, such as a 2A peptide). An LNP carrying different nucleic acids (e.g., mRNA) typically comprises (encapsulates) multiple copies of each nucleic acid. For example, an LNP carrying or encapsulating two different nucleic acids typically carries multiple copies of each of the two different nucleic acids.

[00308] In some embodiments, two or more (e.g., two, three, or four) nucleic acids (e.g., mRNAs), as described herein, encoding different polypeptides, as described herein, are coencapsulated in the same LNP. For example, the LNPs described herein may coencapsulate (a) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a modified MOMP polypeptide, as described herein, (b) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a chimeric VD polypeptide of MOMP, as described herein, and (c) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT443 polypeptide of Chlamydia sp., as described herein. In some embodiments, Petition 870250077861, dated 01 / 09 / 2025, p. 128 / 418 119 / 306 The LNPs described herein coencapsulate (a) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a modified MOMP polypeptide, as described herein, (b) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a chimeric VD polypeptide of MOMP, as described herein, and (d) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT584 polypeptide of Chlamydia sp., as described herein.In some embodiments, the LNPs described herein coencapsulate (a) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a modified MOMP polypeptide, as described herein, (b) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a chimeric VD polypeptide of MOMP, as described herein, (c) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT443 polypeptide of Chlamydia sp., as described herein, and (d) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT584 polypeptide of Chlamydia sp., as described herein.

[00309] Any two nucleic acids (e.g., two mRNAs), as described herein, may be present in a weight ratio of 1:1. Any three nucleic acids (e.g., three mRNAs), as described herein, may be present in a weight ratio of 1:1:1. Any four nucleic acids (e.g., four mRNAs), as described herein, may be present in a weight ratio of 1:1:1. Petition 870250077861, dated 01 / 09 / 2025, page 129 / 418 120 / 306 described in this document may be present in a weight ratio of 1:1:1:1.

[00310] In some embodiments, LNP is as described in this document (e.g., Lipid D or Lipid G).

[00311] Alternatively, any two or more (e.g., four) nucleic acids (e.g., mRNAs) encoding different polypeptides, as described herein, are encapsulated in separate LNPs.

[00312] In some embodiments, a single LNP formulation may comprise multiple types (e.g., two, three, four, five, six, seven, eight, nine, ten or more) of LNPs, wherein each type carries a different nucleic acid (e.g., mRNA).

[00313] When the nucleic acid is mRNA, the mRNA may be unmodified (i.e., containing only the natural ribonucleotides A, U, C, and / or G linked by phosphodiester bonds) or chemically modified 2'-fluoro ribonucleotides (e.g., including nucleotide analogs such as pseudouridines (e.g., N-1-methyl pseudouridine) and 2'-methoxy ribonucleotides and / or phosphorothioate linkages). The mRNA molecule may comprise a 5' cap and a poly(A) tail. G. Buffer and Other Components

[00314] In order to stabilize nucleic acid and / or LNPs (e.g., to extend the shelf life of the vaccine product), facilitate the administration of the LNP pharmaceutical composition and / or enhance in vivo nucleic acid expression, nucleic acid and / or LNP may be formulated in combination with one or more carriers, bleaching agents, stabilizing reagents (e.g., preservatives and antioxidants) and / or other pharmaceutically acceptable excipients. Examples of such excipients are parabens, thimerosal, thimerosal, chlorobutanol, benzalkonium chloride and chelating agents (e.g., EDTA).

[00315] The LNP compositions of the present description may be Petition 870250077861, dated 01 / 09 / 2025, p. 130 / 418 121 / 306 supplied as a frozen liquid form or a freeze-dried form. A variety of cryoprotectants may be used, including, without limitation, sucrose, trehalose, glucose, mannitol, mannose, dextrose and the like. The cryoprotectant may constitute 5-30% (w / v) of the LNP composition. In some embodiments, the LNP composition comprises trehalose, for example, at 5-30% (e.g., 10%) (w / v). Once formulated with the cryoprotectant, the LNP compositions may be frozen (or freeze-dried and cryopreserved) from -20°C to 80°C.

[00316] LNP compositions can be delivered to a patient in an aqueous buffered solution – thawed if previously frozen, or if previously lyophilized, reconstituted in an aqueous buffered solution at the bedside. The buffered solution is preferably isotonic and suitable, for example, for intramuscular or intradermal injection. In some embodiments, the buffered solution is a phosphate-buffered saline (PBS). Nucleic acids

[00317] A nucleic acid of the invention can be RNA or DNA. The nucleic acids of the invention can be single-stranded or double-stranded. In certain embodiments, the nucleic acid is RNA, for example, mRNA. mRNA

[00318] In some embodiments, the nucleic acids of the present invention are messenger RNAs (mRNAs). The mRNAs may be modified or unmodified. The mRNAs may contain one or more coding and non-coding regions. A coding region is alternatively referred to as an open reading frame (ORF). The non-coding regions in an mRNA include the 5' cap, the 5' untranslated region (UTR), the 3' UTR, and a poly(A) tail. An mRNA may be purified from natural sources, produced using recombinant expression systems (e.g., in vitro transcription) Petition 870250077861, dated 01 / 09 / 2025, page 131 / 418 122 / 306 and optionally purified or chemically synthesized.

[00319] In certain embodiments, the mRNA comprises an ORF encoding an antigen of interest. In certain embodiments, the RNA (e.g., mRNA) further comprises at least one 5' UTR, 3' UTR, a poly(A) tail, and / or a 5' cap. In some embodiments, the mRNA comprises (i) a 5' cap as defined herein; (ii) a 5' untranslated region (UTR) as defined herein; (iii) a protein-coding region; (iv) a 3' UTR as defined herein; and (v) a poly(A) tail.Typically, the 3' end of (i) links directly to the 5' end of (ii) via a 3' to 5' phosphodiester bond; the 3' end of (ii) links directly to the 5' end of (iii) via a 3' to 5' phosphodiester bond; the 3' end of (iii) links directly to the 5' end of (iv) via a 3' to 5' phosphodiester bond and the 3' end of (iv) links directly to the 5' end of (v) via a 3' to 5' phosphodiester bond.

[00320] In certain embodiments, mRNA comprises at least one, at least two, at least three, or more stop codons, wherein the stop codons may be selected from UAA, UGA, and UAG, and wherein at least two, at least three, or more stop codons may be identical or different. Typically, the at least one stop codon comprises UAA or UGA (e.g., UAA). Usually, the at least two stop codons comprise at least two identical stop codons, such as UAA or UGA (e.g., UAAUAA or UGAUGA), or at least two different stop codons, which may be selected in particular from UAA and UGA (e.g., UGAUAA). Usually, the at least three stop codons comprise UAA, UGA, and UAG (e.g., UGAUAAUAG). Petition 870250077861, dated 01 / 09 / 2025, p. 132 / 418 123 / 306

[00321] An mRNA sequence is displayed in the 5' to 3' direction unless otherwise indicated. Chapter 5

[00322] A 5' cap of mRNA can provide resistance to nucleases found in most eukaryotic cells and promote translation efficiency. Several types of 5' caps are known. A 7-methylguanosine cap (also called m7G or Cap-0) comprises a guanosine that is linked via a 5'-5' triphosphate bond to the first transcribed nucleotide.

[00323] A 5' cap is typically added as follows: first, a terminal RNA phosphatase removes one of the terminal phosphate groups from the 5' nucleotide, leaving two terminal phosphates; then, guanosine triphosphate (GTP) is added to the terminal phosphates via a guanylyl transferase, producing a 5'5'5-triphosphate linkage; and the 7'-nitrogen of guanine is then methylated by a methyltransferase. Examples of cap structures include, but are not limited to, m7G(5')ppp, (5'(A), G(5')ppp(5')A, and G(5')ppp(5')G. Additional cap structures are described in US Publication No. 2016 / 0032356 and US Publication No. 2018 / 0125989, which are incorporated herein in their entirety by reference.

[00324] 5' capping of polynucleotides can be completed concomitantly during the in vitro transcription reaction using the following RNA cap chemical analogs to generate the 5'-guanosine cap structure according to the manufacturer's protocols: 3'-O-Mem7G(5')ppp(5')G (the ARCA cap); G(5')ppp(5')A; G(5')ppp(5')G; m7G(5')ppp(5')A; m7G(5')ppp(5')G; m7G(5')ppp(5')(2'OMeA)pG; m7G(5')ppp(5')(2'OMeA)pU; m7G(5')ppp(5')(2'OMeG)pG (New England BioLabs, Ipswich, MA; TriLink Biotechnologies). The 5' capping of modified RNA can be completed post-transcriptionally using Petition 870250077861, dated 01 / 09 / 2025, page 133 / 418 124 / 306 of a vaccinia virus capping enzyme to generate the Cap 0 structure: m7G(5')ppp(5')G. The Cap 1 structure can be generated using either the vaccinia virus capping enzyme or a 2'O methyltransferase to generate: m7G(5')ppp(5')G-2'-O-methyl. The Cap 2 structure can be generated from the Cap 1 structure followed by 2'-O-methylation of the antepenultimate nucleotide 5' using a 2'-O methyltransferase. The Cap 3 structure can be generated from the Cap 2 structure followed by 2'-O-methylation of the pre-antepenultimate nucleotide 5' using a 2'-O methyltransferase.

[00325] In certain embodiments, the mRNA of the invention comprises a 5' cap selected from the group consisting of 3'-O-Mem7G(5')ppp(5')G (the ARCA cap), G(5')ppp(5')A, G(5')ppp(5')G, m7G(5')ppp(5')A, m7G(5')ppp(5')G, m7G(5')ppp(5')(2'OMeA)pG, m7G(5')ppp(5')(2'OMeA)pU and m7G(5')ppp(5')(2'OMeG)pG.

[00326] In certain embodiments, the mRNA of the invention comprises a cap 5' of: THE Untranslated Region (UTR)

[00327] In some embodiments, the mRNA of the invention includes a 5' and / or 3' untranslated region (UTR). In the mRNA, the 5' UTR begins at the transcription start site and continues to the start codon, but does not include the start codon. The 3' UTR begins immediately after the stop codon and continues to the transcription termination signal.

[00328] In some embodiments, the mRNA described in this document may comprise a 5' UTR that includes one or more elements that affect the stability or translation of an mRNA. In Petition 870250077861, dated 01 / 09 / 2025, page 134 / 418 125 / 306 In some embodiments, a 5' UTR can be about 10 to 5,000 nucleotides in length. In some embodiments, a 5' UTR can be about 50 to 500 nucleotides in length. In some embodiments, the 5' UTR is at least about 10 nucleotides in length, about 20 nucleotides in length, about 30 nucleotides in length, about 40 nucleotides in length, about 50 nucleotides in length, about 100 nucleotides in length, about 150 nucleotides in length, about 200 nucleotides in length, about 250 nucleotides in length, about 300 nucleotides in length, about 350 nucleotides in length, about 400 nucleotides in length, about 450 nucleotides in length, about 500 nucleotides in length, about 550 nucleotides in length, about 600 nucleotides in length, about 650 nucleotides in length. length, approximately 700 nucleotides in length,approximately 750 nucleotides in length, approximately 800 nucleotides in length, approximately 850 nucleotides in length, approximately 900 nucleotides in length, approximately 950 nucleotides in length, approximately 1,000 nucleotides in length, approximately 1,500 nucleotides in length, approximately 2,000 nucleotides in length, approximately 2,500 nucleotides in length, approximately 3,000 nucleotides in length, approximately 3,500 nucleotides in length, approximately 4,000 nucleotides in length, approximately 4,500 nucleotides in length, or approximately 5,000 nucleotides in length.

[00329] In some embodiments, the mRNA described herein may comprise a 3' UTR comprising one or more of a polyadenylation signal, a binding site for proteins that affect the stability of mRNA localization in a cell, or one or more miRNA binding sites. In some mo Petition 870250077861, dated 01 / 09 / 2025, p. 135 / 418 In 126 / 306 embodiments, a 3' UTR can be 50 to 5,000 nucleotides long or more. In some embodiments, a 3' UTR can be 50 to 1,000 nucleotides long or more.In some embodiments, the 3' UTR is at least about 50 nucleotides long, about 100 nucleotides long, about 150 nucleotides long, about 200 nucleotides long, about 250 nucleotides long, about 300 nucleotides long, about 350 nucleotides long, about 400 nucleotides long, about 450 nucleotides long, about 500 nucleotides long, about 550 nucleotides long, about 600 nucleotides long, about 650 nucleotides long, about 700 nucleotides long, about 750 nucleotides long, about 800 nucleotides long, about 850 nucleotides in length, approximately 900 nucleotides in length, approximately 950 nucleotides in length, approximately 1,000 nucleotides in length, approximately 1,500 nucleotides in length, approximately 2,000 nucleotides in length, approximately 2.500 nucleotides in length, approximately 3,000 nucleotides in length, approximately 3,500 nucleotides in length, approximately 4,000 nucleotides in length, approximately 4,500 nucleotides in length, or approximately 5,000 nucleotides in length.

[00330] In some embodiments, the mRNA described herein may comprise a 5' or 3' UTR that is derived from a gene distinct from that encoded by the mRNA transcript (i.e., the UTR is a heterologous UTR).

[00331] In certain embodiments, the 5' and / or 3' UTR sequences may be derived from mRNAs that are stable (e.g., globin, actin, GAPDH, tubulin, histone, or citric acid cycle enzymes) Petition 870250077861, dated 01 / 09 / 2025, p. 136 / 418 127 / 306 to increase mRNA stability. For example, a 5' UTR sequence may include a partial sequence of an immediate-initiation (IE1) CMV gene 1, or a fragment thereof, to improve resistance to nucleases and / or improve mRNA half-life. The inclusion of a sequence encoding human growth hormone (hGH), or a fragment thereof, at the 3' end or in the untranslated region of the mRNA is also contemplated. Generally, these modifications enhance the stability and / or pharmacokinetic properties (e.g., half-life) of the mRNA relative to its unmodified counterparts and include, for example, modifications made to improve such mRNA resistance to digestion by nucleases in vivo.

[00332] Exemplary 5' UTRs include a sequence derived from an immediate-initiation CMV gene 1 (IE1) (Publications under US Nos. 2014 / 0206753 and 2015 / 0157565, each of which is incorporated herein by reference) or the sequence GGGAUCCUACC (SEQ ID NO: 837) (Publication No. US 2016 / 0151409, incorporated into this document in its entirety by reference).

[00333] In several embodiments, the 5' UTR can be derived from the 5' UTR of a TOP gene. TOP genes are typically characterized by the presence of a 5'-terminal oligopyrimidine tract (TOP). Furthermore, most TOP genes are characterized by growth-associated translational regulation. However, TOP genes with tissue-specific translational regulation are also known. In certain embodiments, the 5' UTR derived from the 5' UTR of a TOP gene lacks the 5' TOP motif (the oligopyrimidine tract) (e.g., US Publications Nos. 2017 / 0029847, 2016 / 0304883, 2016 / 0235864, and 2016 / 0166710, each of which is incorporated herein in its entirety by reference).

[00334] In certain forms, the UTR 5' is derived from a gene Petition 870250077861, dated 01 / 09 / 2025, p. 137 / 418 128 / 306 of the large ribosomal protein 32 (L32) (Publication under No. US 2017 / 0029847, above).

[00335] In certain embodiments, the UTR 5' is derived from the UTR 5' of a hydroxysteroid (17-b) dehydrogenase 4 (HSD17B4) gene (Publication under No. US 2016 / 0166710, supra).

[00336] In certain embodiments, the UTR 5' is derived from the UTR 5' of an ATP5A1 gene (Publication under no. US 2016 / 0166710, supra).

[00337] In some embodiments, an internal ribosome entry site (IRES) is used instead of a 5' UTR.

[00338] In some embodiments, the UTR 5' comprises a nucleic acid sequence set out in SEQ ID NO: 838 and reproduced below: GGACAGAUCGCCUGGAGACGCCAUCCACGCUGUUUUGACCUCC AUAGAAGACACCGGGACCGAUCCAGCCUCCGCGGCCGGGAACG GUGCAUUGGAACGCGGAUUCCCCGUGCCAAGAGUGACUCACCG UCCUUGACACG (SEQ ID NO: 838).

[00339] In some embodiments, UTR 3' comprises a nucleic acid sequence set out in SEQ ID NO: 839 and reproduced below: CGGGUGGCAUCCCUGUGACCCCUCCCCAGUGCCUCUCCUGGCC CUGGAAGUUGCCACUCCAGUGCCCACCAGCCUUGUCCUAAUAAA AUUAAGUUGCAUC (SEQ ID NO: 839).

[00340] UTR 5' and UTR 3' are described in further detail in document no. WO2012 / 075040, which is incorporated herein in its entirety by reference. Polyadenylated Tail

[00341] As used in this document, the terms poly(A) sequence, poly(A) tail, and poly(A) region refer to a sequence of adenosine nucleotides at the 3' end of the mRNA molecule. The poly(A) tail can confer stability to Petition 870250077861, dated 01 / 09 / 2025, p. 138 / 418 129 / 306 mRNA and protect it from degradation by exonucleases. The poly(A) tail can enhance translation. In some embodiments, the poly(A) tail is essentially homopolymeric. For example, a 100-nucleotide adenosine poly(A) tail may be essentially 100 nucleotides long. In certain embodiments, the poly(A) tail may be interrupted by at least one nucleotide other than an adenosine nucleotide (e.g., a nucleotide that is not an adenosine nucleotide). For example, a 100-nucleotide adenosine poly(A) tail may be more than 100 nucleotides long (comprising 100 adenosine nucleotides and at least one nucleotide, or a stretch of nucleotides, that is other than an adenosine nucleotide). In certain modalities, the poly(A) tail comprises the sequence NO:AAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA (SEQ ID NO:840).

[00342] The poly(A) tail, as used in this document, typically refers to RNA. However, in the context of the description, the term similarly refers to corresponding sequences in a DNA molecule (e.g., a poly(T) sequence).

[00343] The poly(A) tail may comprise from about 10 to about 500 adenosine nucleotides, from about 10 to about 200 adenosine nucleotides, from about 40 to about 200 adenosine nucleotides, or from about 40 to about 150 adenosine nucleotides. The length of the poly(A) tail may be at least about 10, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, or 500 adenosine nucleotides. In some embodiments, the poly(A) tail comprises at least 50, at least 75, or at least 100 adenosine nucleotides. Petition 870250077861, dated 01 / 09 / 2025, p. 139 / 418 130 / 306 adenosine.

[00344] In some embodiments where the nucleic acid is RNA, the poly(A) tail of the nucleic acid is obtained from a DNA template during in vitro RNA transcription. In certain embodiments, the poly(A) tail is obtained in vitro by common chemical synthesis methods without being transcribed from a DNA template. In several embodiments, the poly(A) tails are generated by enzymatic polyadenylation of RNA (after in vitro RNA transcription) using commercially available polyadenylation kits and corresponding protocols, or alternatively, using immobilized poly(A)polymerases, for example, using methods and means as described in document no. WO2016 / 174271.

[00345] Nucleic acid may comprise a poly(A) tail obtained by enzymatic polyadenylation, wherein most nucleic acid molecules comprise about 100 (+ / -20) to about 500 (+ / 50) or about 250 (+ / -20) adenosine nucleotides.

[00346] In some embodiments, the nucleic acid may comprise a poly(A) tail derived from a template DNA and may further comprise at least one additional poly(A) tail generated by enzymatic polyadenylation, for example, as described in document no. WO2016 / 091391.

[00347] In certain embodiments, the nucleic acid comprises at least one polyadenylation signal.

[00348] In several embodiments, the nucleic acid may comprise at least one poly(C) sequence.

[00349] The term poly(C) sequence, as used in this document, is intended to be a cytosine nucleotide sequence of up to about 200 cytosine nucleotides. In some embodiments, the poly(C) sequence comprises about 10 to about 200 cytosine nucleotides, about 10 to about 100 cytosine nucleotides. Petition 870250077861, dated 01 / 09 / 2025, p. 140 / 418 131 / 306 cytosine, about 20 to about 70 cytosine nucleotides, about 20 to about 60 cytosine nucleotides, or about 10 to about 40 cytosine nucleotides. In some embodiments, the poly(C) sequence comprises about 30 cytosine nucleotides. Chemical Modification

[00350] The mRNA described herein may be modified or unmodified. Typically, the mRNA comprises at least one chemical modification. In some embodiments, the mRNA described herein may contain one or more modifications that typically enhance RNA stability. Exemplary modifications may include backbone modifications, sugar modifications, or base modifications. In some embodiments, the described mRNA may be synthesized from naturally occurring nucleotides and / or nucleotide analogs (modified nucleotides) including, without limitation, purines (adenine (A) and guanine (G)) or pyrimidines (thymine (T), cytosine (C), and uracil (U)).In certain embodiments, the described mRNA can be synthesized from modified nucleotide analogs or derivatives of purines and pyrimidines, such as, for example, 1-methyladenine, 2-methyladenine, 2-methylthio-N-6-isopentenyladenine, N6-methyladenine, N6-isopentenyladenine, 2-thiocytosine, 3-methylcytosine, 4-acetylcytosine, 5-methylcytosine, 2,6-diaminopurine, 1-methylguanine, 2-methylguanine, 2,2-dimethylguanine, 7-methylguanine, inosine, 1-methylinosine, pseudouracil (5-uracil), dihydrouracil, 2-thiouracil, 4-thiouracil, 5-carboxymethylaminomethyl-2-thiouracil, 5-(carboxyhydroxymethyl)-uracil, 5-fluoro-uracil, 5-bromouracil, 5-carboxymethylaminomethyl-uracil, 5-methyl-2-thio-uracil, 5-methyluracil, N-uracil-5-oxyacetic acid methyl ester, 5-methylaminomethyl-uracil, 5-methoxyaminomethyl-2-thio-uracil, 5'-methoxycarbonylmethyl-uracil, 5-methoxy-uracil, uracil-5-oxyacetic acid methyl ester, uracil-5-oxyacetic acid (v), 1-methyl-pseudouracil. Petition 870250077861, dated 01 / 09 / 2025, page 141 / 418 132 / 306 keosine, β-D-mannosyl-keosine, phosphoramidates, phosphorothioates, peptide nucleotides, methylphosphonates, 7-desaguanosine, 5-methylcytosine and inosine.

[00351] In some embodiments, the described mRNA may comprise at least one chemical modification including, without limitation, pseudouridine, N1-methylpseudouridine, 2-thiouridine, 4'-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-desaza-pseudouridine, 2-thio-1-methylpseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methyluridine, 5-methyluridine, 5-methoxyuridine and 2'-O-methyluridine.

[00352] In some embodiments, the chemical modification is selected from the group consisting of pseudouridine, N1-methylpseudouridine, 5-methylcytosine, 5-methoxyuridine and a combination thereof.

[00353] In some embodiments, the chemical modification comprises N1-methylpseudouridine. Typically, the chemical modification comprises N1-methylpseudouridine. Typically, the chemical modification comprises N1-methylpseudouridine in place of each uridine, i.e., 100% of the U residues are N1-methylpseudouridine.

[00354] In some embodiments, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95% or 100% of the uracil nucleotides in mRNA are chemically modified.

[00355] In some embodiments, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95% or 100% of the uracil nucleotides in the ORF are Petition 870250077861, dated 01 / 09 / 2025, p. 142 / 418 133 / 306 chemically modified.

[00356] The preparation of such analogues is described, for example, in US Patent No. 4,373,071, US Patent No. 4,401,796, US Patent No. 4,415,732, US Patent No. 4,458,066, US Patent No. 4,500,707, US Patent No. 4,668,777, US Patent No. 4,973,679, US Patent No. 5,047,524, US Patent No. 5,132,418, US Patent No. 5,153,319, US Patent No. 5,262,530 and US Patent No. 5,700,642. mRNA synthesis

[00357] The mRNAs described in this document can be synthesized according to any of a variety of known methods. For example, the mRNAs according to this description can be synthesized via in vitro transcription (IVT). Some methods for in vitro transcription are described, for example, in Geall et al. (2013) Semin. Immunol. 25 (2): 152-159; Brunelle et al. (2013) Methods Enzymol. 530: 101-14. Briefly, IVT is typically performed with a linear or circular DNA template containing a promoter, a ribonucleotide triphosphate cluster, a buffer system that may include DTT and magnesium ions, an appropriate RNA polymerase (e.g., T3, T7 or SP6 RNA polymerase), DNase I, pyrophosphatase and / or RNase inhibitor. The exact conditions may vary according to the specific application.The presence of these reagents is generally undesirable in an end mRNA product, and these reagents can be considered impurities or contaminants that can be purified or removed to provide a clean and / or homogeneous mRNA that is suitable for therapeutic use. Although mRNA obtained from in vitro transcription reactions may be desirable in some embodiments, other mRNA sources may be used according to the present description, including wild-type mRNA produced from bacteria, fungi, plants. Petition 870250077861, dated 01 / 09 / 2025, page 143 / 418 134 / 306 tas and / or animals. Processes for Manufacturing Current LNP Compositions

[00358] The present LNPs can be prepared by various techniques currently known in the art. For example, multilamellar vesicles (MLVs) can be prepared according to conventional techniques, such as by depositing a selected lipid on the inner wall of a suitable container or vessel by dissolving the lipid in an appropriate solvent and then evaporating the solvent to leave a thin film inside the vessel, or by spray drying. An aqueous phase can then be added to the vessel with a vortex motion resulting in the formation of MLVs. Unilamellar vesicles (ULVs) can then be formed by homogenization, sonication, or extrusion of multilamellar vesicles. In addition, unilamellar vesicles can be formed by detergent removal techniques.

[00359] Several methods are described in US 2011 / 0244026, US 2016 / 0038432, US 2018 / 0153822, US 2018 / 0125989 and PCT / US2020 / 043223 (filed July 23, 2020) and can be used to practice the present description. An exemplary process involves encapsulating mRNA by mixing it with a mixture of lipids, without first pre-forming the lipids into lipid nanoparticles, as described in US2016 / 0038432. Another exemplary process involves encapsulating mRNA by mixing pre-formed LNPs with mRNA, as described in US2018 / 0153822.

[00360] In some embodiments, the preparation process for mRNA-loaded LNPs includes a heating step of one or more of the solutions to a temperature higher than room temperature, with one or more solutions being the solution comprising the pre-formed lipid nanoparticles, the solution comprising the Petition 870250077861, dated 01 / 09 / 2025, p. 144 / 418135 / 306 mRNA, and the mixed solution comprising the mRNA encapsulated in LNPs. In some embodiments, the process includes the step of heating one or both of the mRNA solutions and the preformed LNP solution before the mixing step. In some embodiments, the process includes heating one or more of the solutions comprising the preformed LNPs, the solution comprising the mRNA, and the solution comprising the LNP-encapsulated mRNA during the mixing step. In some embodiments, the process includes the step of heating the LNP-encapsulated mRNA after the mixing step. In some embodiments, the temperature at which one or more of the solutions are heated is equal to or greater than about 30 °C, 37 °C, 40 °C, 45 °C, 50 °C, 55 °C, 60 °C, 65 °C, or 70 °C. In some embodiments, the temperature at which one or more of the solutions are heated varies from about 25-70 °C, about 30-70 °C, about 35-70 °C, about 40-70 °C, about 45-70 °C, about 50-70 °C or about 60-70 °C.In some disciplines, the temperature is around 65 °C.

[00361] Several methods can be used to prepare a suitable mRNA solution for the present description. In some embodiments, the mRNA can be directly dissolved in a buffer solution described herein. In some embodiments, an mRNA solution can be generated by mixing an mRNA stock solution with a buffer solution before mixing with a lipid solution for encapsulation. In some embodiments, an mRNA solution can be generated by mixing an mRNA stock solution with a buffer solution immediately before mixing with a lipid solution for encapsulation. In some embodiments, a suitable mRNA stock solution may contain mRNA in water or a buffer at a concentration of or greater than about 0.2 mg / ml, 0.4 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.8 mg / ml, 1.0 mg / ml, 1.2 mg / ml, 1.4 mg / ml, 1.5 mg / ml or 1.6 mg / ml, 2.0 mg / ml, 2.5 mg / ml. Petition 870250077861, dated 01 / 09 / 2025, page 145 / 418 136 / 306 mg / ml, 3.0 mg / ml, 3.5 mg / ml, 4.0 mg / ml, 4.5 mg / ml or 5.0 mg / ml.

[00362] In some embodiments, an mRNA stock solution is mixed with a buffer solution using a pump. Exemplary pumps include, but are not limited to, gear pumps, peristaltic pumps, and centrifugal pumps. Typically, the buffer solution is mixed at a higher rate than that of the mRNA stock solution. For example, the buffer solution may be mixed at a rate at least 1x, 2x, 3x, 4x, 5x, 6x, 7x, 8x, 9x, 10x, 15x, or 20x higher than the rate of the mRNA stock solution. In some embodiments, a buffer solution is mixed at a flow rate in a range between approximately 100-6000 ml / minute (for example, approximately 100-300 ml / minute, 300-600 ml / minute, 600-1200 ml / minute, 1200-2400 ml / minute, 2400-3600 ml / minute, 3600-4800 ml / minute, 4800-6000 ml / minute or 60-420 ml / minute).In some embodiments, a buffer solution is mixed at a flow rate of, or greater than, approximately 60 ml / minute, 100 ml / minute, 140 ml / minute, 180 ml / minute, 220 ml / minute, 260 ml / minute, 300 ml / minute, 340 ml / minute, 380 ml / minute, 420 ml / minute, 480 ml / minute, 540 ml / minute, 600 ml / minute, 1200 ml / minute, 2400 ml / minute, 3600 ml / minute, 4800 ml / minute, or 6000 ml / minute.

[00363] In some embodiments, an mRNA stock solution is mixed at a flow rate ranging from about 10-600 mL / minute (e.g., about 5-50 mL / minute, about 10-30 mL / minute, about 30-60 mL / minute, about 60-120 mL / minute, about 120-240 mL / minute, about 240-360 mL / minute, about 360-480 mL / minute, or about 480-600 mL / minute). In some embodiments, a stock solution of mRNA is mixed at a flow rate of or greater than approximately 5 ml / minute, 10 ml / minute, 15 ml / minute, 20 ml / minute, 25 ml / minute, 30 ml / minute, 35 ml / minute, 40 ml / minute, 45 ml / minute, 50 ml / minute, 60 ml / minute, 80 ml / minute, 100 ml / minute, Petition 870250077861, dated 01 / 09 / 2025, page 146 / 418 137 / 306 200 ml / minute, 300 ml / minute, 400 ml / minute, 500 ml / minute or 600 ml / minute.

[00364] The process of incorporating a desired mRNA into a lipid nanoparticle is referred to as loading. Exemplary methods are described in Lasic et al., FEBS Lett. (1992) 312: 255-8. Nucleic acids incorporated into LNPs may be completely or partially located in the interior space of the lipid nanoparticle, within the bilayer membrane of the lipid nanoparticle, or associated with the outer surface of the lipid nanoparticle membrane. The incorporation of an mRNA into lipid nanoparticles is also referred to in this document as encapsulation, where the nucleic acid is wholly or substantially contained within the interior space of the lipid nanoparticle.

[00365] Suitable LNPs can be produced in various sizes. In some embodiments, the reduced size of the lipid nanoparticles is associated with more efficient delivery of mRNA. The selection of an appropriate LNP size may consider the target cell or tissue site and, to some extent, the application for which the lipid nanoparticle is prepared.

[00366] A variety of methods known in the art are available for sizing a population of lipid nanoparticles. Preferred methods in this document utilize Zetasizer Nano ZS (Malvern Panalytical) to measure the particle size of LNPs. In one protocol, 10 μl of an LNP sample are mixed with 990 μl of 10% trehalose. This solution is loaded into a cuvette and then placed in the Zetasizer machine. The average diameter z (nm), or average of the cumulants, is considered as the average size for the LNPs in the sample. The Zetasizer machine can also be used to measure the polydispersity index (PDI) using dynamic light scattering (DLS) and cumulant function analysis. Petition 870250077861, dated 01 / 09 / 2025, page 147 / 418 138 / 306 autocorrelation. The average diameter of LNPs can be reduced by sonication of the formed LNPs. Intermittent sonication cycles can be alternated with quasi-elastic light scattering (QELS) evaluation to guide the efficient synthesis of lipid nanoparticles.

[00367] In some embodiments, most of the purified LNPs, that is, more than about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% of the LNPs, have a size of about 70-150 nm (for example, about 145 nm, about 140 nm, about 135 nm, about 130 nm, about 125 nm, about 120 nm, about 115 nm, about 110 nm, about 105 nm, about 100 nm, about 95 nm, about 90 nm, about 85 nm or about 80 nm). In some embodiments, substantially all (e.g., more than 80 or 90%) of the purified lipid nanoparticles have a size of about 70–150 nm (e.g., about 145 nm, about 140 nm, about 135 nm, about 130 nm, about 125 nm, about 120 nm, about 115 nm, about 110 nm, about 105 nm, about 100 nm, about 95 nm, about 90 nm, about 85 nm, or about 80 nm).

[00368] In some embodiments, the LNPs in the present composition have an average size of less than 150 nm, less than 120 nm, less than 100 nm, less than 90 nm, less than 80 nm, less than 70 nm, less than 60 nm, less than 50 nm, less than 30 nm or less than 20 nm.

[00369] In some embodiments, more than about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% of the LNPs in the present composition have a size in a range of about 4090 nm (e.g., about 45-85 nm, about 50-80 nm, about 55-75 nm or about 60-70 nm) or about 50-70 nm (e.g., 55-65 nm) are particularly suitable for pulmonary delivery by nebulization. Petition 870250077861, dated 01 / 09 / 2025, p. 148 / 418 139 / 306

[00370] In some embodiments, the dispersivity, or measure of heterogeneity in molecule size (PDI), of LNPs in a pharmaceutical composition provided by the present description is less than about 0.5. In some embodiments, an LNP has a PDI of less than about 0.5, less than about 0.4, less than about 0.3, less than about 0.28, less than about 0.25, less than about 0.23, less than about 0.20, less than about 0.18, less than about 0.16, less than about 0.14, less than about 0.12, less than about 0.10, or less than about 0.08. The PDI can be measured by a Zetasizer machine as described above.

[00371] In some embodiments, more than about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the purified LNPs in a pharmaceutical composition provided herein encapsulate an mRNA within each individual particle. In some embodiments, substantially all (e.g., more than 80% or 90% of) purified lipid nanoparticles in a pharmaceutical composition encapsulate an mRNA within each individual particle. In some embodiments, a lipid nanoparticle has an encapsulation efficiency between 50% and 99%; or greater than about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 92%, 95%, 98%, or 99%. Typically, the lipid nanoparticles for use in this document have an encapsulation efficiency of at least 90% (e.g., at least 91, 92, 93, 94, or 95%).

[00372] In some embodiments, an LNP has an N / P ratio between 1 and 10. In some embodiments, a lipid nanoparticle has an N / P ratio above 1, about 1, about 2, about 3, about 4, about 5, about 6, about 7, or about 8. In additional embodiments, a typical LNP in the present document has an N / P ratio of 4. Petition 870250077861, dated 01 / 09 / 2025, p. 149 / 418 140 / 306

[00373] In some embodiments, a pharmaceutical composition according to the present description contains at least about 0.5 μg, 1 μg, 5 μg, 10 μg, 100 μg, 500 μg or 1000 μg of encapsulated mRNA. In some embodiments, a pharmaceutical composition contains from about 0.1 μg to 1000 μg, at least about 0.5 μg, at least about 0.8 μg, at least about 1 μg, at least about 5 μg, at least about 8 μg, at least about 10 μg, at least about 50 μg, at least about 100 μg, at least about 500 μg, or at least about 1000 μg of encapsulated mRNA.

[00374] In some embodiments, mRNA can be produced by chemical synthesis or by in vitro transcription (IVT) of a DNA template. In this process, in an IVT process, a DNA template, such as a cDNA or pDNA template, is used to produce an mRNA transcript, and the DNA template is degraded by a DNase. The transcript is purified by depth filtration and tangential flow filtration (TFF). The purified transcript is further modified by adding a cap and a tail, and the modified RNA is purified again by depth filtration and TFF.

[00375] The mRNA is then prepared in an aqueous buffer and mixed with an amphiphilic solution containing the lipid components of the LNPs. An amphiphilic solution to dissolve the four lipid components of the LNPs can be an alcoholic solution. In some embodiments, the alcohol is ethanol. The aqueous buffer can be, for example, a citrate, phosphate, acetate, or succinate buffer and can have a pH of about 3.0-7.0, for example, about 3.5, about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, or about 6.5. The buffer may contain other components such as a salt (e.g., sodium, potassium, and / or calcium salts). In specific embodiments, the aqueous buffer has 1 mM citrate, 150 mM NaCl, pH 3.5 or 4.5.

[00376] An illustrative process for making a composition Petition 870250077861, dated 01 / 09 / 2025, page 150 / 418 The mRNA-LNP process (141 / 306) involves mixing a buffered mRNA solution with a lipid solution in ethanol in a controlled homogeneous manner, where the lipid:mRNA ratio is maintained throughout the mixing process. In this illustrative example, the mRNA is presented in an aqueous buffer containing citric acid monohydrate, trisodium citrate dihydrate, and sodium chloride. The mRNA solution is added to the solution (1 mM citrate buffer, 150 mM NaCl, pH 4.5). The lipid mixture of four lipids (e.g., a cationic lipid, a PEGylated lipid, a cholesterol-based lipid, and an auxiliary lipid) is dissolved in ethanol. The aqueous mRNA solution and the ethanol and lipid solution are mixed at a volume ratio of 4:1 in a T-mixer with a near-pulseless pump system. The resulting mixture is then subjected to downstream purification and buffer exchange. Buffer exchange can be achieved using dialysis cassettes or a TFF system.TFF can be used to concentrate and buffer the nascent LNP resulting immediately after formation through the T-mixing process. The diafiltration process is a continuous operation, maintaining a constant volume by adding appropriate buffer at the same rate as the permeate flow. Vectors

[00377] In one aspect, vectors comprising a nucleic acid described herein are described herein. In some embodiments, the mRNAs described herein can be cloned into a vector. Vectors include, but are not limited to, a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid. Vectors also include expression vectors, replication vectors, probe generation vectors, sequencing vectors, and vectors optimized for in vitro transcription (IVT). Petition 870250077861, dated 01 / 09 / 2025, page 151 / 418 142 / 306

[00378] In certain modalities, the vector can be used to express mRNA in a host cell. In several modalities, the vector can be used as a template for IVT. The ideally translated IVT mRNA construct suitable for therapeutic use is described in detail in Sahin, et al. (2014). Nat. Rev. Drug Discov. 13, 759-780; Weissman (2015). Expert Rev. Vaccines 14, 265-281.

[00379] In some embodiments, the vectors described herein may comprise at least the following, from 5' to 3': an RNA polymerase promoter; a polynucleotide sequence encoding a 5' UTR; a polynucleotide sequence encoding an ORF; a polynucleotide sequence encoding a 3' UTR; and a polynucleotide sequence encoding at least one RNA aptamer. In some embodiments, the vectors described herein may comprise a polynucleotide sequence encoding a poly(A) sequence and / or a polyadenylation signal.

[00380] A variety of RNA polymerase promoters are known. In some embodiments, the promoter may be a T7 RNA polymerase promoter. Other useful promoters may include, but are not limited to, T3 and SP6 RNA polymerase promoters. Consensus nucleotide sequences are known for the T7, T3, and SP6 promoters.

[00381] Host cells (e.g., mammalian cells, e.g., human cells) comprising the vectors or nucleic acids described herein are also described in this document. A host cell includes an individual cell or cell culture that may be or has been a recipient of exogenous nucleic acid. Host cells include the progeny of a single host cell, and the progeny may not necessarily be completely identical (in morphology or in full complement of Petition 870250077861, dated 01 / 09 / 2025, page 152 / 418 143 / 306 DNA) to the original mother cell due to mutation and / or natural, accidental or deliberate change. Host cells include cells transfected or infected in vivo or in vitro with nucleic acid or vector described in this document.

[00382] Vectors can be introduced into target cells using any of a number of different methods, for example, commercially available methods which include, but are not limited to, electroporation (Amaxa Nucleofector-II (Amaxa Biosystems, Cologne, Germany)), (ECM 830 (BTX) (Harvard Instruments, Boston, Mass.) or Gene Pulser II (BioRad, Denver, Colorado), Multiporator (Eppendorf, Hamburg, Germany), cationic liposome-mediated transfection using lipofection, polymer encapsulation, peptide-mediated transfection, biolistic particle delivery systems such as gene guns (see, for example, Nishikawa, et al. (2001). Hum Gene Ther. 12 (8): 861-70 or the TransIT-RNA transfection kit (Mirus, Madison, WI).

[00383] Chemical means of introducing a vector into a host cell include colloidal dispersion systems such as macromolecule complexes, nanocapsules, microspheres, spherules, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. An exemplary colloidal system for use as an in vitro and in vivo delivery vehicle is a liposome (e.g., artificial membrane vesicle).

[00384] Regardless of the method used to introduce exogenous nucleic acids into a host cell or otherwise expose a cell to the inhibitor of the present description, in order to confirm the presence of the mRNA sequence in the host cell, a variety of assays can be performed. Self-replicating RNA, Trans-replicating RNA and Non-replicating RNA

[00385] Typically, the nucleic acid molecules described in Petition 870250077861, dated 01 / 09 / 2025, page 153 / 418 144 / 306 of this document are non-replicating RNAs. However, the nucleic acid molecules described in this document may alternatively be self-replicating RNAs or trans-replicating RNAs. Self-replicating RNA

[00386] Self-replicating or (self-amplifying) RNA can be produced using replication elements derived from, for example, alphaviruses, and replacing the structural viral proteins with a nucleotide sequence encoding a protein of interest (e.g., a Chlamydia sp. antigen). A self-replicating RNA is typically a positive-strand molecule that can be directly translated after delivery to a cell, and this translation provides an RNA-dependent RNA polymerase that then produces both antisense and sense transcripts from the delivered RNA. In this way, the delivered RNA results in the production of multiple daughter RNAs. These daughter RNAs, as well as collinear subgenomic transcripts, can themselves be translated to provide in situ expression of an encoded antigen or can be transcribed to provide additional transcripts with the same sense as the delivered RNA that are translated to provide in situ expression of the antigen.The overall result of this sequence of transcripts is a large amplification in the number of introduced replicon RNAs, and thus the encoded antigen becomes a major polypeptide product of the cells.

[00387] A suitable system for achieving self-replication in this way is to use an alphavirus-based replicon. These replicons are positive-strand (positive-sense) RNA that result in translation by a replicase (or replicase-transcriptase) after delivery to a cell. The replicase is translated as a polyprotein that self-cleaves to provide a replication complex that creates genomic strand copies of the delivered positive-strand RNA. These negative-strand (-) transcripts can themselves be the transcripts to generate additional copies. Petition 870250077861, dated 01 / 09 / 2025, page 154 / 418 145 / 306 positive-strand parent RNA and also to generate a subgenomic transcript encoding the antigen. Translation of the subgenomic transcript thus leads to in situ expression of the antigen by the infected cell. Suitable alphavirus replicons can use a replicase from a Sindbis virus, a Semliki forest virus, an eastern equine encephalitis virus, a Venezuelan equine encephalitis virus, etc. Mutant or wild-type virus sequences can be used, for example, the attenuated TC83 mutant of VEEV has been used in replicons, see the following reference: Document No. WO2005 / 113782, incorporated herein in its entirety by reference.

[00388] In one embodiment, each self-replicating RNA described herein encodes (i) an RNA-dependent RNA polymerase that can transcribe RNA from the self-replicating RNA molecule and (ii) a Chlamydia sp. antigen. The polymerase may be an alphavirus replicase, for example, comprising one or more of the alphavirus proteins nsP1, nsP2, nsP3, and nsP4. While natural alphavirus genomes encode virion structural proteins in addition to the non-structural replicase polyprotein, in certain embodiments, the self-replicating RNA molecules do not encode alphavirus structural proteins. Thus, the self-replicating RNA may result in the production of genomic RNA copies of the same in a cell, but not in the production of RNA-containing virions. The inability to produce these virions means that, unlike a wild-type alphavirus, the self-replicating RNA molecule cannot perpetuate itself in infectious form.The structural proteins of alphaviruses that are necessary for perpetuation in wild-type viruses are absent from the self-replicating RNAs of the present description, and their place is taken by a gene (or genes) that encodes the immunogen of interest, so that the subgenomic transcript encodes the immunogen instead. Petition 870250077861, dated 01 / 09 / 2025, page 155 / 418 146 / 306 of the structural proteins of alphavirus virions. Self-replicating RNAs are described in further detail in document no. WO2011005799, which is incorporated herein in its entirety by reference. Trans-Replicating RNA

[00389] Transreplicating (or transamplifying) RNA has elements similar to the self-replicating RNA described above. However, with transreplicating RNA, two separate RNA molecules are used. A first RNA molecule encodes the RNA replicase described above (e.g., alphavirus replicase) and a second RNA molecule encodes the protein of interest (e.g., an antigenic Chlamydia sp. antigen described in this document). The RNA replicase can replicate one or both of the first and second RNA molecules, thus greatly increasing the number of copies of RNA molecules encoding the protein of interest. Transreplicating RNAs are described in further detail in document no. WO2017162265, which is incorporated herein in its entirety by reference. Trans-Replicating RNA

[00390] Non-replicating (or non-amplifying) RNA is RNA that lacks the ability to replicate. Therapeutic uses

[00391] In another aspect, the invention provides the polypeptides, nucleic acids, combinations or compositions of the present invention for use as a medicament. The invention also provides for the use of the polypeptides, nucleic acids, combinations or compositions of the present invention for the manufacture of a medicament. The medicament can be used to treat or prevent a disease as described herein. The invention also provides a method of treating or preventing a disease, comprising administering Petition 870250077861, dated 01 / 09 / 2025, p. 156 / 418 147 / 306 traction of polypeptides, nucleic acids, combinations or compositions of the present invention to an individual who needs them. The polypeptides, nucleic acids, combinations or compositions of the present invention can, for example, be administered in an effective quantity to treat or prevent disease in the individual. Polypeptides, nucleic acids, combinations or compositions can therefore be administered in an effective quantity. Typically, the treatment is prophylactic.

[00392] In another aspect, the invention provides the polypeptides, nucleic acids, combinations or compositions of the present invention for use in the treatment or prevention of a Chlamydia sp. infection in an individual (e.g., a human). The invention also provides the use of the polypeptides, nucleic acids, combinations or compositions of the present invention for the manufacture of a medicament to treat or prevent a Chlamydia sp. infection in an individual (e.g., a human). The invention also provides a method for treating or preventing a Chlamydia sp. infection in an individual (e.g., a human), wherein the method comprises administering the polypeptides, nucleic acids, combinations or compositions of the present invention to the individual. The polypeptides, nucleic acids, combinations or compositions of the present invention may, for example, be administered in an amount effective to treat or prevent a Chlamydia sp. infection.in the individual (i.e., administered in an effective amount). Polypeptides, nucleic acids, combinations, or compositions can be used to generate an immune response against Chlamydia sp. infection in an individual (e.g., human). In preferred embodiments, the infection is a C. trachomatis infection.

[00393] The invention provides the polypeptides, nucleic acids, combinations or compositions of the present invention for use in the tra Petition 870250077861, dated 01 / 09 / 2025, page 157 / 418 148 / 306 Treatment or prevention of trachoma (an eye disease caused by C. trachomatis infection), genital tract infection by Chlamydia trachomatis, lymphogranuloma venereum (a disease caused by C. trachomatis), oropharyngeal infection by C. trachomatis, or rectal infection by C. trachomatis in an individual (e.g., human). The invention also provides the use of the polypeptides, nucleic acids, combinations, or compositions of the present invention for the manufacture of a medicament to treat or prevent trachoma caused by C. trachomatis infection, genital tract infection by Chlamydia trachomatis, lymphogranuloma venereum (a disease caused by C. trachomatis), oropharyngeal infection by C. trachomatis, or rectal infection by C. trachomatis in an individual (e.g., human). The invention also provides a method of treating or preventing trachoma caused by C. trachomatis infection.trachomatis, genital tract infection caused by Chlamydia trachomatis, lymphogranuloma venereum caused by C. trachomatis infection, oropharyngeal infection caused by C. trachomatis, or rectal infection caused by C. trachomatis in an individual (e.g., a human being), wherein the method comprises administering the polypeptides, nucleic acids, combinations, or compositions of the present invention to the individual. The polypeptides, nucleic acids, combinations, or compositions of the present invention may, for example, be administered in an amount effective to treat or prevent trachoma caused by C. trachomatis infection, genital tract infection caused by Chlamydia trachomatis, lymphogranuloma venereum caused by C. trachomatis infection, oropharyngeal infection caused by C. trachomatis, or rectal infection caused by C. trachomatis in the individual (i.e., administered in an effective amount). In preferred embodiments, the infection is a C. trachomatis infection.Trachoma can be caused by infection with serovars A, B, Ba, or C of C. trachomatis. Lymphogranuloma venereum can be caused by infection with serovars L1, L2, and L3 of C. trachomatis. Petition 870250077861, dated 01 / 09 / 2025, p. 158 / 418 149 / 306 C. trachomatis. Genital tract infection can be caused by DK serovars. In preferred embodiments, Chlamydia sp. (e.g., C. trachomatis) is a genital tract infection.

[00394] The invention provides the polypeptides, nucleic acids, combinations or compositions of the present invention for use in a method of providing protective immunity against a Chlamydia sp. infection in an individual (e.g., a human). The invention also provides the use of the polypeptides, nucleic acids, combinations or compositions of the present invention for the manufacture of a medicament for use in a method of providing protective immunity against a Chlamydia sp. infection in an individual (e.g., a human). The invention further provides a method for providing protective immunity against a Chlamydia sp. infection in an individual (e.g., a human), wherein the method comprises administering the polypeptides, nucleic acids, combinations or compositions of the present invention to the individual.The polypeptides, nucleic acids, combinations or compositions of the present invention can, for example, be administered in an effective amount to provide protective immunity against a Chlamydia sp. infection in the individual (i.e., administered in an effective amount). In preferred embodiments, the infection is a C. trachomatis infection.

[00395] The polypeptides, nucleic acids, combinations or compositions of the invention can elicit a T cell response (e.g., an antigen-specific T cell response) in an individual. The polypeptides, nucleic acids, combinations or compositions of the invention can elicit a CD4+ T cell response and / or a CD8+ T cell response (e.g., a CD4+ T cell response) in an individual. In some embodiments, the polypeptides, nucleic acids, combinations or compositions of the invention Petition 870250077861, dated 01 / 09 / 2025, page 159 / 418 150 / 306 can induce IFNγ-producing T cells, such as IFNγ-producing CD4+ T cells and / or IFNγ-producing CD8+ T cells (e.g., IFNγ-producing CD4+ T cells) in an individual. In some embodiments, the polypeptides, nucleic acids, combinations, or compositions of the invention can induce IFNγ+IL2+TNFα+ CD4+ T cells (i.e., CD4+ T cells that produce IFNγ, IL2, and TNFα). In some embodiments, the polypeptides, nucleic acids, combinations, or compositions of the invention can induce IFNγ+IL2-TNFα+ CD8+ T cells or CD8+ T cells that produce IFNγ and TNFα. In some embodiments, the polypeptides, nucleic acids, combinations or compositions of the invention may elicit a cross-serovar T-cell immune response in an individual, that is, a T-cell immune response that is cross-reactive against two or more serovars of Chlamydia sp. (e.g., cross-reactive against two or more serovars of C. trachomatis).The production of cytokines by T cells can be measured by intracellular cytokine staining of T cells, for example, T cells obtained from an individual, or by detecting secreted cytokines (for example, by ELISA). The polypeptides, nucleic acids, combinations, or compositions of the invention can elicit a Th1 response (for example, a Th1 T cell response) in an individual.

[00396] The polypeptides, nucleic acids, combinations or compositions of the invention can elicit an antibody response (e.g., IgG) in an individual, such as a neutralizing antibody response (IgG). The antibodies can be of any isotype (e.g., IgA, IgG, IgM, i.e., an α, γ or μ heavy chain), but will generally be IgG. Within the IgG isotype, the antibodies can be of the IgG1, IgG2, IgG3 or IgG4 subclass. The antibody may have a κ or λ light chain. A neutralizing antibody is an antibody that neutralizes the biological effects of a Chlamydia sp. antigen in an individual. Petition 870250077861, dated 01 / 09 / 2025, p. 160 / 418 151 / 306 duo. In some embodiments, the polypeptides, nucleic acids, combinations or compositions of the invention may elicit an antibody response between serovars in an individual, that is, an antibody response that is cross-reactive against two or more serovars of Chlamydia sp. (for example, cross-reactive against two or more serovars of C. trachomatis).

[00397] In some embodiments, the polypeptides, nucleic acids, combinations or compositions of the invention may elicit a T cell response, as described herein, and / or an antibody response, as described herein.

[00398] Administration of a polypeptide, nucleic acid, combination or composition of the invention to an individual may enable the individual to produce a population of CD4 memory T cells responsive to Chlamydia sp. antigen or a population of CD8 memory T cells (e.g., CD4 memory T cell population) upon exposure to Chlamydia sp. bacteria or Chlamydia sp. antigen. The population of CD4 memory T cells responsive to Chlamydia sp. may confer sterilizing immunity (i.e., complete protective immunity) against reinfection.

[00399] Administration of a polypeptide, nucleic acid, combination or composition of the invention to an individual may enable the individual to produce a population of Chlamydia sp. antigen-responsive memory B cells upon exposure to Chlamydia sp. bacteria or Chlamydia sp. antigen. The population of Chlamydia sp.-responsive memory B cells may confer sterilizing immunity (i.e., complete protective immunity) against reinfection.

[00400] The polypeptides, nucleic acids, combinations or compositions of the invention can be used to induce a primary immune response and / or to enhance an immune response. Petition 870250077861, dated 01 / 09 / 2025, page 161 / 418 152 / 306

[00401] The polypeptides, nucleic acids, combinations or compositions of the invention can be administered to an individual to enable the individual to develop and / or maintain sterilizing immunity to a Chlamydia sp infection. Protective immunity can be provided or enhanced in an immunized individual following a Chlamydia sp infection.

[00402] The polypeptides, nucleic acids, combinations or compositions of the invention can be used in a primary-booster vaccination regimen. Protective immunity against a Chlamydia sp. infection according to the invention can be provided by administering a vaccine preparation comprising a polypeptide, nucleic acid, combination or composition of the invention, followed by a booster vaccine. The booster vaccine can be the same as the primary vaccine.

[00403] In certain embodiments, the individual is a vertebrate, for example, a mammal, such as a human being or a veterinary mammal (e.g., cat, dog, horse, cow, sheep, cattle, deer, goat, pig, rodents (e.g., mice)). In preferred embodiments, the individual is a human being. The individual (e.g., the human individual) may be male or female. In some embodiments, human subjects may be 7 to 50 (e.g., 9 to 44) years old. Routes of administration

[00404] The polypeptides, nucleic acids, combinations or compositions of the present invention may be administered parenterally (for example, intramuscularly, intradermally, subcutaneously, intraperitoneally, intravenously or into the interstitial space of a tissue) or by rectal, oral, vaginal, topical, transdermal, intranasal, sublingual, ocular, auditory, pulmonary or other mucosal administration. In some embodiments, the compositions of the invention Petition 870250077861, dated 01 / 09 / 2025, page 162 / 418 153 / 306 are administered intramuscularly. In some embodiments, the compositions of the invention are administered via the mucosa.

[00405] In certain embodiments, a polypeptide, nucleic acids, combinations or composition (e.g., a composition) of the invention are provided for use in intramuscular (IM) injection. The polypeptide, nucleic acids, combinations or composition (e.g., composition) can be administered into the thigh or upper arm of an individual, for example, into the deltoid muscle in the upper arm. In some embodiments, the polypeptide, nucleic acids, combinations or composition (e.g., composition) are provided in a pre-filled syringe or injector (e.g., single-chamber or multi-chamber). The injection can be made using a needle (e.g., a hypodermic needle), but needle-free injection can also be used. A typical intramuscular dose is 0.5 ml.In some embodiments, the polypeptide, nucleic acids, combinations or composition (e.g., the composition) are provided for inhalation use and are supplied in a pre-filled pump, aerosolizer or inhaler.

[00406] In certain embodiments, a polypeptide, nucleic acids, combinations or composition (e.g., a composition) of the invention are provided for use in skin injection, for example, into the epidermis, dermis or hypodermis of the skin. In some embodiments, the composition is provided in a device suitable for skin injection, such as a needle (e.g., an epidermal, dermal or hypodermal needle), a needle-free device, a microneedle device or a microprojection array device. Examples of microneedle or microprojection array devices suitable for cutaneous injection according to the invention are described in documents no. US20230270842A1, US20220339416A1, US20210085598A1, US20200246450A1, US20220143376A1, Petition 870250077861, dated 01 / 09 / 2025, page 163 / 418 154 / 306 US20180264244A1, US20180263641A1 and US20110245776A1.

[00407] The compositions of the invention can be used to induce systemic and / or mucosal immunity.

[00408] Dosage treatment may be a single-dose or multiple-dose regimen. Multiple doses (e.g., two or three) may be used in a primary immunization schedule and / or a booster immunization schedule. A primary dose schedule may be followed by a booster dose schedule. Multiple doses (e.g., two or three doses) will typically be administered at least 1 week apart (e.g., approximately 2 weeks, approximately 3 weeks, approximately 4 weeks, approximately 6 weeks, approximately 8 weeks, approximately 10 weeks, approximately 12 weeks, approximately 16 weeks, etc.) to individuals in need of them to achieve the desired therapeutic or prophylactic effects.Doses (e.g., initial and booster doses) may be separated by an interval of, for example, 1 week, 2 weeks, 3 weeks, 4 weeks, one month, two months, three months, four months, five months, six months, one year, two years, five years, or ten years

[00409] . A composition of the invention may be in the form of an extemporaneous formulation, for example, a composition of the invention may be lyophilized. Such compositions may be reconstituted with a physiological buffer (e.g., PBS) immediately before use. The compositions of the invention may be supplied in the form of an aqueous solution or a frozen aqueous solution and may be administered directly to individuals without reconstitution (after thawing, if previously frozen).

[00410] In some embodiments of a composition comprising an mRNA as described in this document, a single dose of the composition contains 1 to 400 pg, such as 1-50 μg, of an mRNA as described in this document (e.g., mo Petition 870250077861, dated 01 / 09 / 2025, p. 164 / 418 155 / 306 novalent or multivalent). For example, a single dose may contain approximately 2.5 μg, approximately 5 μg, approximately 7.5 μg, approximately 10 μg, approximately 12.5 μg, or approximately 15 μg of an mRNA described in this document, for example, for intramuscular (IM) injection.

[00411] In some embodiments, the composition comprises two nucleic acids (e.g., two mRNAs), as described herein, encoding different polypeptides, as described herein, and the nucleic acids are present in a weight ratio of 1:1. In some embodiments, the composition comprises three nucleic acids (e.g., three mRNAs), as described herein, encoding different polypeptides, as described herein, and the nucleic acids are present in a weight ratio of 1:1:1.Typically, the LNPs described herein coencapsulate (a) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a modified MOMP polypeptide, as described herein, (b) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a chimeric VD polypeptide of MOMP, as described herein, (c) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT443 polypeptide of Chlamydia sp., as described herein, and (d) a nucleic acid, as described herein, comprising a nucleotide sequence encoding a CT584 polypeptide of Chlamydia sp., as described herein.Typically, the composition comprises four nucleic acids (e.g., four mRNAs), as described herein, which encode different polypeptides, as described herein. Typically, the nucleic acids are... Petition 870250077861, dated 01 / 09 / 2025, page 165 / 418 156 / 306 are present in a weight ratio of 1:1:1:1.

[00412] In further embodiments, a composition of the invention may be provided as a single multivalent dose containing multiple (e.g., 2, 3 or 4) types of LNPs, each for a different antigen, and each type of LNP has an mRNA quantity of, for example, 2.5 μg, about 5 μg, about 7.5 μg, about 10 μg, about 12.5 μg or about 15 μg.

[00413] In some embodiments, the individual receives one or more nucleic acid compositions of the present invention. The nucleic acid compositions may comprise a nucleic acid comprising a nucleotide sequence encoding a polypeptide antigen as described herein. The nucleic acid compositions may be administered simultaneously, separately, or sequentially. In some embodiments, the individual receives a combination of nucleic acids of the present invention. Combinations of nucleic acids include combinations of two or more nucleic acids as described herein. The nucleic acids within a combination may be administered simultaneously, separately, or sequentially.

[00414] In some embodiments, the individual receives one or more polypeptide compositions of the present invention. The polypeptide compositions may comprise a polypeptide antigen, as described herein. The polypeptide compositions may be administered simultaneously, separately, or sequentially. In some embodiments, the individual receives a combination of polypeptides of the present invention. Polypeptide combinations include combinations of two or more polypeptides, as described herein. The nucleic acids within a combination may be administered simultaneously, separately, or sequentially. Petition 870250077861, dated 01 / 09 / 2025, page 166 / 418 157 / 306

[00415] In some embodiments, the individual receives one or more nucleic acid compositions of the present invention and one or more polypeptide compositions of the invention. In some embodiments, the individual receives a nucleic acid composition comprising a nucleotide sequence encoding a modified MOMP polypeptide (and, optionally, a nucleic acid composition comprising a nucleotide sequence encoding a chimeric VD polypeptide of MOMP) and a polypeptide composition comprising one or more polypeptides comprising a polypeptide sequence of a non-MOMP antigen. In some embodiments, the individual receives two or more polypeptide compositions, each comprising a polypeptide comprising a polypeptide sequence of a non-MOMP antigen. The nucleic acid composition and one or more polypeptide compositions may be administered simultaneously, separately, or sequentially.

[00416] Compositions administered separately or sequentially may be administered within 12 months of each other, within six months of each other, or within one month or less of each other (e.g., within 10 days). Compositions may be administered within 7 days, within 3 days, within 2 days, or within 24 hours of each other. Simultaneous administration may involve administering the compositions of the invention at the same time. Simultaneous administration may include administering the compositions of the invention to a patient within 12 hours of each other, within 6 hours, within 3 hours, within 2 hours, or within 1 hour of each other, typically during the same visit to a clinical center.

[00417] The present invention also provides a kit comprising one or more compositions described herein in one or more containers or provides one or more compositions as described herein. Petition 870250077861, dated 01 / 09 / 2025, page 167 / 418 158 / 306 me described in this document in one or more containers and a physiological buffer for reconstitution in another container. The container (or containers) may contain a single-use dose or a multi-use dose. The container may be pre-treated glass vials or ampoules. The kit may include instructions for use.

[00418] A method for the detection and quantification of antibodies against one or more of the polypeptides described in this document in a serum sample is also provided herein. For example, antibodies against MOMP, CT443 and / or CT584 polypeptides can be detected and quantified. The detection and quantification of antibodies against each polypeptide can be performed separately or simultaneously, for example, as a panel in a single multi-well plate. Thus, a multi-well plate comprising wells coated with each of the recombinant polypeptides MOMP, CT443 and CT584 is further provided herein. Definitions

[00419] The term comprising encompasses including and also consisting, for example, a composition comprising X may consist exclusively of X or may include something additional, for example, X + Y.

[00420] The term about in relation to a numerical value x is optional and means, for example, x+ / -10%.

[00421] The term one or more entities refers to one or more of these entities: for example, a nucleotide sequence is understood as representing one or more nucleotide sequences. Thus, the terms one, one or more, and at least one may be used interchangeably in this document.

[00422] Furthermore, and / or, when used in this document Petition 870250077861, dated 01 / 09 / 2025, p. 168 / 418 159 / 306 to, should be taken as a specific description of each of the two specified characteristics or components with or without the other. Thus, the term and / or, as used in a phrase such as A and / or B in this document, includes A and B, A or B, A (alone) and B (alone). Similarly, the term and / or as used in a phrase such as A, B and / or C is intended to encompass each of the following aspects: A, B and C; A, B or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[00423] The term Chlamydia sp. as used in this document refers to species of the genus Chlamydia, which comprises the species Chlamydia trachomatis, Chlamydia abortus, Chlamydia pneumoniae, Chlamydia muridarum, Chlamydia psittaci, Chlamydia pecorum, Chlamydia felis and Chlamydia caviae. In preferred embodiments of the invention, Chlamydia sp. is C. trachomatis.

[00424] As used in this document, the term effective amount refers to a quantity (e.g., of a nucleic acid, a polypeptide, a combination or a composition as described in this document) sufficient to produce beneficial or desired results. An effective amount may be administered in one or more administrations, applications or dosages, and is not intended to be limited to a specific formulation or route of administration. The term effective amount includes, for example, therapeutically effective amount and / or prophylactically effective amount.The term "effective amount," as used herein, refers to an amount (for example, of a nucleic acid, a polypeptide, a combination or a composition, as described herein) that is effective in producing some desired therapeutic or prophylactic effects in the treatment or prevention of an infection, disease, disorder and / or condition at a reasonable benefit / risk ratio applicable to any medical treatment. Petition 870250077861, dated 01 / 09 / 2025, page 169 / 418 160 / 306 co.

[00425] The term elementary body refers to one of the forms of the bacterium Chlamydia sp. Elementary bodies can be released from infected cells and can be transmitted from one individual to another.

[00426] The term fragment or variant, when referring to the polypeptides of the present description, includes any polypeptides that retain at least some of the properties (e.g., specific antigenic property of the polypeptide or the ability of the polypeptide to contribute to the induction of antibody binding) of the reference polypeptide. Polypeptide fragments include N-terminal and / or C-terminal truncated fragments, for example, C-terminal fragments and N-terminal fragments, as well as deletion fragments, but do not include the naturally occurring full-length polypeptide (or mature polypeptide). A deletion fragment refers to a polypeptide with 1 or more internal amino acids omitted from the full-length polypeptide. Polypeptide variants include fragments, as described above, and also polypeptides with altered amino acid sequences due to amino acid substitutions, deletions, or insertions.Variants can occur naturally or not. Variants that do not occur naturally can be produced using mutagenesis techniques known in the art. Variant polypeptides may comprise conservative or non-conservative amino acid substitutions, deletions, or additions. Such variations (i.e., amino acid truncations and / or substitutions, deletions, or insertions) may occur at the amino acid level or correspondingly at the nucleic acid level.

[00427] Identity with respect to a sequence is defined in this document as the percentage of naked acid residues. Petition 870250077861, dated 01 / 09 / 2025, page 170 / 418 161 / 306 cleico or amino acids in the candidate sequence that are identical to the reference amino acid sequence after sequence alignment and the introduction of gaps, if necessary, to achieve the maximum percentage of sequence identity, and not considering any conservative substitutions as part of the sequence identity.

[00428] Sequence identity can be determined by standard methods commonly used to compare the similarity in amino acid position of two polypeptides or nucleic acids of two polynucleotides. For example, using a computer program such as BLAST or FASTA, two polypeptides are aligned for optimal matching of their respective amino acids (along the entire length of one or both sequences or along a predetermined portion of one or both sequences). The programs provide a standard gap penalty and a standard gap penalty, and a scoring matrix such as PAM 250 [a standard scoring matrix; see Dayhoff et al., in Atlas of Protein Sequence and Structure, vol. 5, supp. 3 (1978)] can be used in conjunction with the computer program.The percentage of identity can be calculated as: the total number of identical matches multiplied by 100 and then divided by the sum of the length of the longest sequence within the matching interval and the number of gaps introduced in the shorter sequences to align the two sequences.

[00429] As used in this document, the term kit refers to a packaged set of related components, such as one or more compounds or compositions and one or more related materials such as solvents, solutions, buffers, instructions or desiccants.

[00430] The term attached or linked, as used in the present Petition 870250077861, dated 01 / 09 / 2025, page 171 / 418 162 / 306 of the document refers to a first amino acid sequence or nucleotide sequence covalently linked to a second amino acid sequence or nucleotide sequence, respectively (for example, a secretory signal peptide amino acid sequence and / or a heterologous transmembrane domain amino acid sequence linked to a Chlamydia sp. polypeptide amino acid sequence). The first amino acid or nucleotide sequence may be directly linked to the second amino acid or nucleotide sequence or, alternatively, an intermediate sequence may covalently link the first sequence to the second sequence.The term linked means not only a fusion of a first amino acid sequence to a second amino acid sequence at the C-terminus or N-terminus, but also includes the insertion of the entire first amino acid sequence (or the second amino acid sequence) into any two amino acids in the second amino acid sequence (or the first amino acid sequence, respectively). In one embodiment, the first amino acid sequence may be linked to a second amino acid sequence by a peptide bond or a linker. The first nucleotide sequence may be linked to a second nucleotide sequence by a phosphodiester bond or a linker. The linker may be a peptide or a polypeptide (for polypeptide chains) or a nucleotide or a nucleotide chain (for nucleotide chains) or any chemical fraction (for polypeptide and polynucleotide chains). The term linked is also indicated by a hyphen (-).

[00431] The term native, as used in this document, refers to sequences that occur naturally. For example, a native Chlamydia sp. MOMP polypeptide is a naturally occurring Chlamydia sp. MOMP polypeptide. Modalities Petition 870250077861, dated 01 / 09 / 2025, page 172 / 418 163 / 306

[00432] The invention includes at least the following numbered embodiments:

[00433] 1. A nucleic acid comprising a nucleotide sequence encoding a modified Major Outer Membrane Protein (MOMP) polypeptide, wherein the modified MOMP polypeptide has an amino acid sequence comprising two or more conserved domain sequences of a native Chlamydia sp MOMP polypeptide and a non-native loop sequence between the conserved domain sequences;

[00434] 2. The nucleic acid of modality 1, in which the Chlamydia sp. is Chlamydia trachomatis.

[00435] 3. The nucleic acid of embodiment 1 or 2, in which the modified MOMP polypeptide does not comprise a native Chlamydia sp. MOMP variable domain between the two or more conserved domain sequences.

[00436] 4. The nucleic acid of any of the modalities 1-3, wherein the modified MOMP polypeptide comprises five conserved domain sequences of a native Chlamydia sp. MOMP polypeptide, optionally wherein (i) the modified MOMP polypeptide comprises all five conserved full-length domains of a native Chlamydia sp. MOMP polypeptide. (ii) the conserved domain sequences of the polypeptide Modified MOMPs are at least 95% identical to a conserved domain of a native MOMP polypeptide from a Chlamydia sp. of any serovar (for example, a conserved domain as defined in Table 1); (iii) the conserved domains of the modified MOMP polypeptide collectively have at least 95% sequence identity with the conserved domains of a native MOMP polypeptide (by Petition 870250077861, dated 01 / 09 / 2025, p. 173 / 418 164 / 306 example, serovar E MOMP); and / or (iv) the conserved domain sequences of the polypeptide The modified MOMP lacks up to 3 or 5 amino acids of a conserved MOMP domain sequence from a native Chlamydia species.

[00437] 5. The nucleic acid of any of the modalities 1-4, wherein (i) the modified MOMP polypeptide comprises a non-native loop sequence between each of the conserved domain sequences; (ii) the non-native loop sequence is no more than 40% identical to any native VD sequence of Chlamydia sp. from any serovar (e.g., serovars D, E, F, or G of C. trachomatis).

[00438] 6. The nucleic acid of embodiment 4, in which the modified MOMP polypeptide comprises four non-native loop sequences and does not comprise any native Chlamydia sp. MOMP variable domain among the conserved domain sequences.

[00439] 7. The nucleic acid of any of the modalities 1-6, wherein the modified MOMP polypeptide does not comprise any native Chlamydia sp. MOMP variable domain between any of the conserved domain sequences.

[00440] 8. The nucleic acid of any of the modalities 1-7, wherein (i) the non-native loop sequence is between 3 and 30 amino acids long, for example, between 4 and 20 amino acids long and / or (ii) the two or more conserved domain sequences are linked by a non-native loop sequence such that the conserved domain sequences form a beta-barrel structure (for example Petition 870250077861, dated 01 / 09 / 2025, page 174 / 418 165 / 306 plo, composed of antiparallel beta ribbons), optionally wherein the beta barrel structure is as predicted in silico (e.g., using Alphafold2 software (Deepmind)).

[00441] 9. The nucleic acid of any of the modalities 1-8, where (i) a non-native handle sequence that replaces VD1 comprises a sequence according to SEQ ID NO: 462 or 466 (e.g., SEQ ID NO: 462); (i) a non-native handle sequence that replaces VD2 comprises a sequence with SEQ ID NO: 463 or 467 (e.g., SEQ ID NO:463); (iii) a non-native loop sequence that replaces VD3 comprises a sequence according to SEQ ID NOs 464 or 468 (e.g., SEQ ID NO: 464); and / or (iv) a non-native loop sequence that replaces VD4 comprises a sequence according to SEQ ID NO: 465 or 469 (e.g., SEQ ID NO: 465), for example, wherein the modified MOMP polypeptide comprises four non-native loop sequences according to SEQ ID NOs 462, 463, 464 and 465 in place of VD1, VD2, VD3 and VD4, respectively.

[00442] 10. The nucleic acid of any of the modalities 1-9, wherein the modified MOMP polypeptide comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in a conserved domain sequence of a native Chlamydia sp. MOMP polypeptide, optionally wherein the single amino acid substitution is a cysteine-to-serine substitution.

[00443] 11. The nucleic acid of any of the modalities 1-10, wherein the modified MOMP polypeptide comprises a mu Petition 870250077861, dated 01 / 09 / 2025, p. 175 / 418 166 / 306 mutation in one or more (e.g., all) positions corresponding to a glycosylation site, optionally an N-glycosylation site, in a native Chlamydia sp. MOMP polypeptide, optionally wherein the mutation is a single amino acid substitution.

[00444] 12. The nucleic acid of any of the modalities 1-11, wherein the modified MOMP polypeptide further comprises a secretion signal peptide sequence.

[00445] 13. The nucleic acid of embodiment 12, wherein the secretion signal peptide sequence is a viral secretion signal peptide sequence, optionally selected from the group consisting of: an influenza hemagglutinin (HA) secretion signal peptide sequence, a SARS-CoV-2 spike secretion signal peptide sequence, a VZV gB secretion signal peptide sequence, a VZV gE secretion signal peptide sequence, a VZV gI secretion signal peptide sequence, a VZV gK secretion signal peptide sequence, a measles protein F secretion signal peptide sequence, a rubella protein E1 secretion signal peptide sequence, a rubella protein E2 secretion signal peptide sequence, a mumps protein F secretion signal peptide sequence, an Ebola protein GP secretion signal peptide sequence, and a 6kDa IC protein secretion signal peptide sequence. smallpox,optionally where the secretory signal peptide sequence comprises an amino acid sequence according to one of the SEQ ID NOs in Table 2 or Table 2.1.,

[00446] 14. The nucleic acid of embodiment 13, wherein the secretion signal peptide sequence comprises a secretion signal peptide sequence of the HA protein of influenza A virus, for example, wherein the secretion signal peptide sequence comprises a sequence according to SEQ ID NO: 187 or SEQ ID Petition 870250077861, dated 01 / 09 / 2025, page 176 / 418 167 / 306 NO: 188.

[00447] 15. The nucleic acid of any of the modalities 1-14, wherein the modified MOMP polypeptide comprises a sequence according to any of the SEQ ID NOs: 486-489 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it, for example, wherein the modified MOMP polypeptide comprises a sequence according to SEQ ID NO: 486 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it.

[00448] 16. The nucleic acid of any of the modalities 1-15, wherein the nucleic acid comprises a nucleotide sequence according to any of the SEQ ID NOs: 551-566 or a sequence that has at least 50% identity with it, for example, wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 551 or a sequence that has at least 50% (e.g., at least 75%) identity with it.

[00449] 17. The nucleic acid of any of the modalities 1-16, wherein the nucleic acid is characterized by the fact that it is a messenger RNA (mRNA), optionally wherein (i) the mRNA comprises at least one 5' untranslated region (UTR 5'), at least one 3' untranslated region (UTR 3') and / or at least one polyadenylation sequence (poly(A)); (ii) the mRNA is not modified or comprises at least one chemical modification, optionally wherein the mRNA comprises at least one chemical modification, for example, wherein the chemical modification comprises N1-methylpseudouridine and / or (iii) the mRNA is a self-replicating mRNA or a non-replicating mRNA, for example, a non-replicating mRNA.

[00450] 18. The nucleic acid of modality 17, in which the Petition 870250077861, dated 01 / 09 / 2025, page 177 / 418 168 / 306 mRNA comprises or consists of (for example, consisting of) the following structural elements: - a chapter 5', for example, a chapter with the following structure: THE - an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; - a protein-coding region having the nucleic acid sequence according to SEQ ID NO: 213; - an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO: 839 and - a poly(A) tail.

[00451] 19. The nucleic acid of embodiment 18, in which the mRNA is chemically modified and in which the chemical modification comprises or consists of (for example, consists of) N1-methylpseudouridine in place of each uridine.

[00452] 20. A polypeptide of Major Membrane Protein A modified external MOMP that has an amino acid sequence comprising two or more conserved domain sequences from a native Chlamydia sp. MOMP polypeptide and a non-native loop sequence between the conserved domain sequences.

[00453] 21. Modified MOMP polypeptide modality 20, in which the modified MOMP polypeptide does not comprise a native Chlamydia sp. MOMP variable domain between the two or more conserved domain sequences.

[00454] 22. Modified MOMP polypeptide of modality 20 Petition 870250077861, dated 01 / 09 / 2025, page 178 / 418 169 / 306 or 21, wherein the modified MOMP polypeptide comprises five conserved domain sequences of a native Chlamydia sp. MOMP polypeptide, optionally wherein (i) the modified MOMP polypeptide comprises all five conserved full-length domains of a native Chlamydia sp. MOMP polypeptide and / or (ii) the conserved domains of the modified MOMP polypeptide collectively have at least 95% sequence identity with the conserved domains of a native MOMP polypeptide (e.g., serovar E MOMP).

[00455] 23. The modified MOMP polypeptide of any of the embodiments 20-22, wherein the modified MOMP polypeptide comprises a non-native loop sequence between each of the conserved domain sequences.

[00456] 24. Modified MOMP polypeptide modality 22, in which the modified MOMP polypeptide comprises four non-native loop sequences and does not include any native Chlamydia sp. MOMP variable domains among the conserved domain sequences.

[00457] 25. The modified MOMP polypeptide of any of the embodiments 20-24, wherein the modified MOMP polypeptide does not comprise any native Chlamydia sp. MOMP variable domain between any of the conserved domain sequences.

[00458] 26. The modified MOMP polypeptide of any of the embodiments 20-25, in which the non-native loop sequence is between 3 and 30 amino acids in length, for example, between 4 and 20 amino acids in length.

[00459] 27. The modified MOMP polypeptide of any of embodiments 20-26, wherein (i) a non-native loop sequence replacing VD1 comprises a sequence according to SEQ ID NO: 462 or 466 (by Petition 870250077861, dated 01 / 09 / 2025, p. 179 / 418 170 / 306 example, SEQ ID NO: 462); (i) a non-native handle sequence that replaces VD2 comprises a sequence with SEQ ID NO: 463 or 467 (e.g., SEQ ID NO:463); (iii) a non-native loop sequence that replaces VD3 comprises a sequence according to SEQ ID NOs 464 or 468 (e.g., SEQ ID NO: 464); and / or (iv) a non-native loop sequence that replaces VD4 comprises a sequence according to SEQ ID NO: 465 or 469 (e.g., SEQ ID NO: 465), for example, wherein the modified MOMP polypeptide may comprise four non-native loop sequences according to SEQ ID NOs 462-465 in place of VD1, VD2, VD3 and VD4, respectively.

[00460] 28. The modified MOMP polypeptide of any of the embodiments 20-27, wherein the modified MOMP polypeptide comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in a conserved domain sequence of a native Chlamydia sp. MOMP polypeptide, optionally wherein the single amino acid substitution is a cysteine-to-serine substitution;

[00461] 29. The modified MOMP polypeptide of any of the embodiments 20-28, wherein the modified MOMP polypeptide comprises a mutation at one or more (e.g., all) positions corresponding to an N-glycosylation site in a native Chlamydia sp. MOMP polypeptide, optionally wherein the mutation is a single amino acid substitution;

[00462] 30. The modified MOMP polypeptide of any of the embodiments 20-29, wherein the modified MOMP polypeptide comprises a sequence according to any of the SEQ ID Nos: 486-489 or a sequence that has at least 70% (by Petition 870250077861, dated 01 / 09 / 2025, page 180 / 418 171 / 306 example, at least 90 or 95%) identity with the same, for example, wherein the modified MOMP polypeptide comprises a sequence according to SEQ ID NO: 486 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with the same.

[00463] 31. A composition comprising nucleic acid of any of the embodiments 1-19, preferably wherein the composition is an immunogenic composition.

[00464] 32. A composition comprising the polypeptide of any of the 20-30 embodiments, preferably wherein the composition is an immunogenic composition.

[00465] 33. The composition of modality 31, in which the composition also includes: (i) a nucleic acid comprising a nucleotide sequence encoding a chimeric variable domain (VD) polypeptide of Chlamydia sp. MOMP, wherein the chimeric VD polypeptide of MOMP comprises an amino acid sequence comprising two or more VD sequences of Chlamydia sp. MOMP from different serovars of Chlamydia sp. and / or (ii) one or more (for example, one, two, three or four) of: (a) a nucleic acid comprising a nucleotide sequence encoding a CT443 polypeptide from Chlamydia sp.; (b) a nucleic acid comprising a nucleotide sequence encoding a CT584 polypeptide from Chlamydia sp.; (c) a nucleic acid comprising a nucleotide sequence encoding a CT600 polypeptide from Chlamydia sp. and (d) a nucleic acid comprising a nucleotide sequence encoding a CT812 polypeptide from Chlamydia sp.

[00466] 34. The composition of modality 33, in which the composition comprises Petition 870250077861, dated 01 / 09 / 2025, page 181 / 418 172306 the nucleic acid of (i) and the nucleic acid of (ii)(a); the nucleic acid of (i) and the nucleic acid of (ii)(b); or the nucleic acid of (i), the nucleic acid of (ii)(a) and the nucleic acid of (ii)(b); for example, wherein the composition comprises the nucleic acid of (i), the nucleic acid of (ii)(a) and the nucleic acid of (ii)(b).

[00467] 35. The composition of embodiment 33 or 34, in which one or more nucleic acids are an mRNA, optionally in which (i) the mRNA comprises at least one 5' untranslated region (UTR 5'), at least one 3' untranslated region (UTR 3') and / or at least one polyadenylation sequence (poly(A)); (ii) the mRNA is not modified or comprises at least one chemical modification, optionally wherein the mRNA comprises at least one chemical modification, for example, wherein the chemical modification comprises N1-methylpseudouridine and / or (iii) the mRNA is a self-replicating mRNA or a non-replicating mRNA, for example, a non-replicating mRNA.

[00468] 36. The composition of any of the embodiments 31 or 33-35, wherein the composition further comprises a lipid nanoparticle (LNP), optionally in which the nucleic acid is encapsulated in the LNP.

[00469] 37. The composition of modality 32, in which the composition also includes: (i) a chimeric variable domain (VD) polypeptide of (i) MOMP of Chlamydia sp., wherein the chimeric VD polypeptide of MOMP comprises an amino acid sequence comprising two or more VD sequences of MOMP from Chlamydia sp. of different serovars of Chlamydia sp. and / or (ii) one or more (e.g., one, two, three or four) of: (a) a polypeptide comprising the amino acid sequence Petition 870250077861, dated 01 / 09 / 2025, page 182 / 418 173 / 306 acids of a CT443 polypeptide from Chlamydia sp.; (b) a polypeptide comprising the amino acid sequence of a CT584 polypeptide from Chlamydia sp.; (c) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT600 polypeptide or (d) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT812 polypeptide, for example, wherein the composition comprises the polypeptide of (i) and the polypeptide of (ii)(a); or the polypeptide of (i) and the polypeptide of (ii)(b); or the polypeptide of (i), the polypeptide of (ii)(a) and the polypeptide of (ii)(b), for example, wherein the composition comprises the polypeptide of (i), the polypeptide of (ii)(a) and the polypeptide of (ii)(b).

[00470] 38. The composition of any of the modalities 33-37, where Chlamydia sp. is Chlamydia trachomatis.

[00471] 39. The composition of any of the modalities 33-38, wherein the chimeric VD polypeptide of MOMP comprises conserved domain sequence portions of a native Chlamydia sp. MOMP polypeptide flanking each of the two or more VD sequences of MOMP.

[00472] 40. The composition of any of the modalities 33-39, wherein the chimeric polypeptide VD of MOMP comprises VD sequences of MOMP from four different serovars, optionally wherein the different serovars are selected from serovars D, E, F or G of C. trachomatis.

[00473] 41. The composition of any of the modalities 33-40, wherein the chimeric polypeptide VD of MOMP comprises: (i) two MOMP VD1 sequences from different serovars of Chlamydia sp. and / or Petition 870250077861, dated 01 / 09 / 2025, p. 183 / 418 174 / 306 (ii) two VD2 sequences of MOMP from different serovars of Chlamydia sp. and / or (iii) a MOMP VD3 sequence and / or (iv) two MOMP VD4 sequences from different serovars of Chlamydia sp., optionally, in which the different serovars are selected from among the D, E, F, or G serovars of C. trachomatis.

[00474] 42. The composition of any of the modalities 33-40, wherein the chimeric polypeptide VD of MOMP comprises a VD sequence of MOMP from serovar D or E of C. trachomatis and a VD sequence of MOMP from serovar F or G of C. trachomatis.

[00475] 43. The composition of embodiment 41 or 42, in which the chimeric polypeptide VD of MOMP comprises at least one (for example, four) of (i)-(iv): (i) a VD1 sequence of MOMP from serovar D and a VD1 sequence of MOMP from serovar F or a VD1 sequence of MOMP from serovar E and a VD1 sequence of MOMP from serovar F or G (for example, a VD1 sequence of MOMP from serovar E and a VD1 sequence of MOMP from serovar G) and / or (ii) a VD2 sequence of MOMP from serovar E and a VD2 sequence of MOMP from serovar F or a VD2 sequence of MOMP from serovar D and a VD2 sequence of MOMP from serovar G (for example, a VD2 sequence of MOMP from serovar D and a VD2 sequence of MOMP from serovar G) and / or (iii) a VD3 sequence of MOMP from serovar G or a VD3 sequence from serovar F (for example, serovar F) and / or (iv) a VD4 sequence of MOMP from serovar E and a VD4 sequence of MOMP of serovar G or a VD4 sequence of MOMP of serovar D and a VD4 sequence of MOMP of serovar F (for example, a VD4 sequence of MOMP of serovar D and a se Petition 870250077861, dated 01 / 09 / 2025, p. 184 / 418 175 / 306 sequence VD4 of MOMP of serovar F), where serovars D, E, F or G are of C. trachomatis.

[00476] 44. The composition of embodiment 43, in which the chimeric polypeptide VD of MOMP comprises: (i) a VD1 MOMP sequence from serovar D and a VD1 MOMP sequence from serovar F, a VD2 MOMP sequence from serovar E and a VD2 MOMP sequence from serovar F, a VD3 MOMP sequence from serovar G, a VD4 MOMP sequence from serovar E and a VD4 MOMP sequence from serovar G or (ii) a VD1 MOMP sequence from serovar E and a VD1 MOMP sequence from serovar F, a VD2 MOMP sequence from serovar D and a VD2 MOMP sequence from serovar G, a VD3 MOMP sequence from serovar F, a VD4 MOMP sequence from serovar D and a VD4 MOMP sequence from serovar F, wherein serovars D, E, F or G are from C. trachomatis, for example, wherein the chimeric polypeptide VD of MOMP comprises VD of MOMP sequences according to (ii).

[00477] 45. The composition of any of the embodiments 39 to 44, in which the conserved domain sequence portions are conserved domain sequence portions of a Chlamydia sp. native MOMP polypeptide that flanks the VD in its Chlamydia sp. native MOMP polypeptide.

[00478] 46. The composition of any of the modalities 39-45, wherein each conserved domain sequence portion comprises between 3 and 30 amino acid residues of a conserved domain sequence of a native Chlamydia sp. MOMP polypeptide, wherein the between 3 and 30 amino acid residues are immediately adjacent to the VD sequence in its native Chlamydia sp. MOMP polypeptide.

[00479] 47. The composition of any of the modalities Petition 870250077861, dated 01 / 09 / 2025, page 185 / 418 176 / 306 33-36 or 38-46, wherein the composition comprises nucleic acid comprising a nucleotide sequence encoding a chimeric VD polypeptide of Chlamydia sp. MOMP and wherein the chimeric VD polypeptide of MOMP comprises a secretion signal peptide sequence.

[00480] 48. The composition of embodiment 47, in which the secretion signal peptide sequence is a viral secretion signal peptide sequence, optionally selected from the group consisting of: an influenza hemagglutinin (HA) secretion signal peptide sequence, a SARS-CoV-2 spike secretion signal peptide sequence, a VZV gB secretion signal peptide sequence, a VZV gE secretion signal peptide sequence, a VZV gI secretion signal peptide sequence, a VZV gK secretion signal peptide sequence, a measles protein F secretion signal peptide sequence, a rubella protein E1 secretion signal peptide sequence, a rubella protein E2 secretion signal peptide sequence, a mumps protein F secretion signal peptide sequence, an Ebola protein GP secretion signal peptide sequence, and a 6kDa IC protein secretion signal peptide sequence. smallpox,optionally where the secretory signal peptide sequence comprises an amino acid sequence in accordance with any of the SEQ ID NOs in Table 2 or Table 2.1.

[00481] 49. The composition of embodiment 48, wherein the secretion signal peptide sequence comprises a secretion signal peptide sequence of the HA protein of influenza A virus, for example, wherein the secretion signal peptide sequence comprises a sequence according to SEQ ID NO: 187 or SEQ ID NO: 188.

[00482] 50. The composition of any of the modalities Petition 870250077861, dated 01 / 09 / 2025, page 186 / 418 177 / 306 33-49, wherein the chimeric VD polypeptide of MOMP comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in a conserved domain sequence of a native Chlamydia sp. MOMP polypeptide, optionally wherein the single amino acid substitution is a cysteine-to-serine substitution.

[00483] 51. The composition of any of the modalities 33-50, wherein the chimeric VD polypeptide of MOMP comprises a mutation at one or more (e.g., all) positions corresponding to a glycosylation site, optionally an N-glycosylation site, in a native Chlamydia sp. MOMP polypeptide, optionally wherein the mutation is a single amino acid substitution.

[00484] 52. The composition of embodiment 51, in which the chimeric polypeptide VD of MOMP comprises a single amino acid substitution at each of the amino acid residues corresponding to position 9 of SEQ ID NO: 9 (e.g., substitution of N for A), position 11 of SEQ ID NO: 17 (e.g., substitution of T for A), position 17 of SEQ ID NO: 6 (e.g., substitution of S for A), positions 4 and 21 of SEQ ID NO: 18 (e.g., substitutions of N for A and S for A, respectively), position 14 of SEQ ID NO: 8 (e.g., a substitution of T for A) and position 14 in SEQ ID NO: 16 (e.g., substitution of T for A).

[00485] 53. The composition of any of the modalities 33-52, wherein the chimeric polypeptide VD of MOMP comprises a sequence according to any of the SEQ ID Nos: 490505 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it, for example, wherein the chimeric polypeptide VD of MOMP comprises a sequence Petition 870250077861, dated 01 / 09 / 2025, p. 187 / 418 178 / 306 according to SEQ ID NO: 503 or a sequence that has at least 70% (for example, at least 90 or 95%) identity with it.

[00486] 54. The composition of any of the modalities 33-36 or 38-53, wherein the composition comprises nucleic acid comprising a nucleotide sequence encoding a chimeric VD polypeptide of Chlamydia sp. MOMP and wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 567-630 or a sequence having at least 50% (e.g., at least 75%) identity therewith, for example, wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 617 or a sequence having at least 50% (e.g., at least 75%) identity therewith.

[00487] 55. The composition of any of the modalities 33-36 or 38-54, wherein the composition comprises one or more nucleic acids from (ii)(a)-(d) and wherein Chlamydia sp. polypeptide CT443, Chlamydia sp. polypeptide CT584, Chlamydia sp. polypeptide CT600 and Chlamydia sp. polypeptide CT812 comprise a secretion signal peptide sequence.

[00488] 56. The composition of embodiment 55, in which the secretion signal peptide sequence is a viral secretion signal peptide sequence, optionally selected from the group consisting of: an influenza hemagglutinin (HA) secretion signal peptide sequence, a SARS-CoV-2 spike secretion signal peptide sequence, a VZV gB secretion signal peptide sequence, a VZV gE secretion signal peptide sequence, a VZV gI secretion signal peptide sequence, a VZV gK secretion signal peptide sequence, a measles F protein secretion signal peptide sequence, a sequence Petition 870250077861, dated 01 / 09 / 2025, pages 188 / 418 179 / 306 of a rubella protein E1 secretion signal peptide, a rubella protein E2 secretion signal peptide sequence, a mumps protein F secretion signal peptide sequence, an Ebola protein GP secretion signal peptide sequence, and a smallpox protein 6kDa IC secretion signal peptide sequence, optionally wherein the secretion signal peptide sequence comprises an amino acid sequence in accordance with one of the SEQ ID NOs in Table 2 or Table 2.1.

[00489] 57. The composition of embodiment 56, wherein the secretion signal peptide sequence comprises a secretion signal peptide sequence of the HA protein of influenza A virus, for example, wherein the secretion signal peptide sequence comprises a sequence according to SEQ ID NO: 187 or SEQ ID NO: 188.

[00490] 58. The composition of any of the modalities 55-57, wherein one or more of the Chlamydia sp. CT443, Chlamydia sp. CT584, Chlamydia sp. CT600, or Chlamydia sp. CT812 polypeptides comprise a heterologous transmembrane domain.

[00491] 59. The composition of embodiment 58, in which the transmembrane domain sequence is selected from the group consisting of: an influenza hemagglutinin (HA) transmembrane domain sequence, a SARS-CoV-2 spike transmembrane domain sequence, a VZV gB transmembrane domain sequence, a VZV gE transmembrane domain sequence, a VZV gI transmembrane domain sequence, a VZV gK transmembrane domain sequence, a measles F protein transmembrane domain sequence, a rubella E1 protein transmembrane domain sequence, a rubella E2 protein transmembrane domain sequence, a mumps F protein transmembrane domain sequence, and a transmembrane domain sequence Petition 870250077861, dated 01 / 09 / 2025, page 189 / 418 180 / 306 transmembrane domain of the Ebola GP protein, optionally wherein the transmembrane domain comprises an amino acid sequence according to one of the SEQ ID NOs in Table 3.

[00492] 60. The composition of embodiment 58 or 59, wherein the transmembrane domain comprises the sequence of a transmembrane domain of the HA protein of influenza A virus, for example, wherein the transmembrane domain comprises a sequence according to SEQ ID NO: 813 or SEQ ID NO: 814.

[00493] 61. The composition of any of the modalities 33-60, wherein one or more of the Chlamydia sp. polypeptide CT443, the Chlamydia sp. polypeptide CT584, the Chlamydia sp. polypeptide CT600 and the Chlamydia sp. polypeptide CT812 comprise a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in the respective native Chlamydia sp. polypeptide, optionally wherein the single amino acid substitution is a cysteine ​​substitution for serine.

[00494] 62. The composition of any of the modalities 33-61, wherein one or more of the Chlamydia sp. CT443, Chlamydia sp. CT584, Chlamydia sp. CT600 or Chlamydia sp. CT812 polypeptides comprises a mutation at one or more (e.g., all) positions corresponding to an N-glycosylation site in the respective native Chlamydia sp. polypeptide, optionally wherein the mutation is a single amino acid substitution.

[00495] 63. The composition of embodiment 62, in which the Chlamydia sp. polypeptide CT584 comprises a single amino acid substitution at a position corresponding to residue 11 of SEQ ID NO: 509 (e.g., a substitution from N to Q).

[00496] 64. The composition of any of the modalities 33-63, in which Petition 870250077861, dated 01 / 09 / 2025, pp. 190 / 418 181 / 306 (a) the Chlamydia sp. CT443 polypeptide comprises a sequence according to SEQ ID NO: 507-508 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it, for example, wherein the Chlamydia sp. CT443 polypeptide comprises a sequence according to SEQ ID NO: 507 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it; (b) the Chlamydia sp. polypeptide CT584 comprises a sequence according to any of SEQ ID NO: 509-512 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it, for example, wherein the Chlamydia sp. polypeptide CT584 comprises a sequence according to any of SEQ ID NO: 510 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it; (c) the Chlamydia sp. polypeptide CT600 comprising a sequence according to any of SEQ ID NO: 513-514 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it and / or (d) the Chlamydia sp. polypeptide CT812 comprising a sequence according to any of SEQ ID NO: 515-535 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it.

[00497] 65. The composition of any of the modalities 33-36 and 38-64, in which the composition comprises: (1) MOMP's VD chimeric polypeptide comprises a sequence conforming to any of the SEQ ID NO: 490-505 (e.g., SEQ ID NO: 503) or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it; (2) nucleic acid comprising a sequence of nucleotides Petition 870250077861, dated 01 / 09 / 2025, p. 191 / 418 182 / 306 encoding a chimeric VD polypeptide of Chlamydia sp. MOMP comprises a nucleotide sequence according to SEQ ID NO: 567-630 (e.g., SEQ ID NO: 617) or a sequence that has at least 50% identity with it; (3) the CT443 polypeptide from Chlamydia sp. comprises a sequence according to SEQ ID NO: 507 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it; (4) the nucleic acid comprising a nucleotide sequence encoding the CT443 polypeptide of Chlamydia sp. comprises a nucleotide sequence according to any of the SEQ ID NO: 707-710 (e.g., SEQ ID NO: 707) or a sequence that has at least 50% (e.g., at least 75%) identity with it; (5) the CT584 polypeptide of Chlamydia sp. comprises a sequence conforming to any of SEQ ID NO: 509-512 (e.g., SEQ ID NO: 510) or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it; (6) the nucleic acid comprising a nucleotide sequence encoding the Chlamydia sp. CT584 polypeptide comprises a nucleotide sequence according to any of the SEQ ID NO: 711-718 (e.g., SEQ ID NO: 715) or a sequence that has at least 50% (e.g., at least 75%) identity with it; (7) the Chlamydia sp. CT600 polypeptide comprising a sequence according to any of SEQ ID NO: 513-514 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it and / or (8) the nucleic acid comprising a nucleotide sequence encoding the Chlamydia sp. CT600 polypeptide comprising a Petition 870250077861, dated 01 / 09 / 2025, p. 192 / 418 183 / 306 nucleotide sequence matching any of the SEQ ID NO: 719-722 or a sequence that has at least 50% (e.g., at least 75%) identity with it; (9) the Chlamydia sp. CT812 polypeptide comprises a sequence according to any of the SEQ ID NO: 515-535 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity therewith; and / or (10) the nucleic acid comprising a nucleotide sequence encoding the Chlamydia sp. CT812 polypeptide comprises a nucleotide sequence according to any of the SEQ ID NO: 723-762 or a sequence that has at least 50% (e.g., at least 75%) identity therewith; optionally in which: the nucleic acids of (ii)(a), wherein the nucleic acid of (ii)(a) comprises a nucleotide sequence according to SEQ ID NO: 707 or a sequence that has at least 50% (at least 75%) identity with it and / or the nucleic acid of (ii)(b), wherein the nucleic acid of (ii)(b) comprises a nucleotide sequence according to SEQ ID NO: 715 or a sequence that has at least 50% (at least 75%) identity with it.

[00498] 66. The composition of any of the modalities 33-36 or 38-65, wherein the nucleic acid of (ii)(a) is an mRNA and the mRNA comprises or consists of (e.g., consists of) the following structural elements: - a chapter 5, for example, a chapter 5 with the following structure: Petition 870250077861, dated 01 / 09 / 2025, p. 193 / 418 184 / 306 O - an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; - a protein-coding region having the nucleic acid sequence according to SEQ ID NO:369; - an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO:839 and - a poly(A) tail.

[00499] 67. The composition of any of the modalities 33-36 or 38-66, wherein the nucleic acid of (ii)(b) is an mRNA and the mRNA comprises or consists of (for example, consists of) the following structural elements: - a chapter 5, for example, a chapter 5 with the following structure: the - an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; - a protein-coding region having the nucleic acid sequence according to SEQ ID NO:377; - an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO: 839 and - a poly(A) tail. Petition 870250077861, dated 01 / 09 / 2025, page 194 / 418 185 / 306

[00500] 68. The composition of embodiment 54, wherein the nucleic acid comprising a nucleotide sequence encoding a chimeric VD polypeptide of Chlamydia sp. MOMP is an mRNA and the mRNA comprises or consists of (e.g., consists of) the following structural elements: - a chapter 5, for example, a chapter 5 with the following structure: - an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; - a protein-coding region having the nucleic acid sequence according to SEQ ID NO:870; - an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO: 839 and a poly(A) tail.

[00501] 69. The composition of any of the modalities 33-36 and 38-68, in which the composition comprises: (1) the nucleic acid (e.g., mRNA) of embodiment 16, wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 551 or a sequence that has at least 50% (e.g., at least 75%) identity with it (e.g., wherein the nucleic acid is an mRNA of embodiment 18 or 19); The nucleic acid (e.g., mRNA) comprises a nucleotide sequence encoding the chimeric polypeptide VD of Chlamydia sp., where...

Claims

CLAIMS 1. Composition, characterized in that it comprises (i) a nucleic acid comprising a nucleotide sequence encoding a modified Major Outer Membrane Protein (MOMP) polypeptide, wherein the modified MOMP polypeptide has an amino acid sequence comprising two or more conserved domain sequences of a native Chlamydia trachomatis MOMP polypeptide and a non-native loop sequence between the conserved domain sequences; (ii) a nucleic acid comprising a nucleotide sequence encoding a chimeric variable domain (VD) polypeptide of Chlamydia trachomatis MOMP,wherein the chimeric VD polypeptide of MOMP comprises an amino acid sequence comprising two or more VD sequences of Chlamydia trachomatis MOMP from different serovars of Chlamydia trachomatis; (iii) a nucleic acid comprising a nucleotide sequence encoding a CT443 polypeptide of Chlamydia trachomatis; and (iv) a nucleic acid comprising a nucleotide sequence encoding a CT584 polypeptide of Chlamydia trachomatis.

2. Nucleic acid, characterized in that it comprises a nucleotide sequence encoding a modified Major Outer Membrane Protein (MOMP) polypeptide, wherein the modified MOMP polypeptide has an amino acid sequence comprising two or more conserved domain sequences of a native Chlamydia sp. MOMP polypeptide. and a non-native loop sequence between the preserved domain sequences Petition 870250077861, dated 01 / 09 / 2025, page 317 / 418 2 / 46 of,Optionally, the Chlamydia sp. is Chlamydia trachomatis.

3. Modified Main Outer Membrane Protein (MOMP) polypeptide, characterized in that it has an amino acid sequence comprising two or more conserved domain sequences of a native Chlamydia sp. MOMP polypeptide and a non-native loop sequence between the conserved domain sequences, optionally wherein the Chlamydia sp. is Chlamydia trachomatis.

4. Composition according to claim 1, nucleic acid according to claim 2, or modified MOMP polypeptide according to claim 3, characterized in that the non-native loop sequence is no more than 40% identical to any VD (VD1, VD2, VD3 or VD4) sequence of native Chlamydia sp. MOMP of any serovar (e.g., serovars D, E, F or G of C. trachomatis).

5. Composition according to claim 1 or 4, nucleic acid according to claim 2 or 4,or the modified MOMP polypeptide according to claim 3 or 4, characterized in that the modified MOMP polypeptide: (1) does not comprise a variable domain of native Chlamydia sp. MOMP between the two or more conserved domain sequences; and / or (2) comprises five conserved domain sequences of a native Chlamydia sp. MOMP polypeptide, optionally wherein (i) the modified MOMP polypeptide comprises all five conserved full-length domains of a native Chlamydia sp. MOMP polypeptide and / or (ii) the conserved domains of the modified MOMP polypeptide collectively have at least 95% sequence identity with the conserved domains of a native MOMP polypeptide (e.g., serovar E MOMP). Petition 870250077861, dated 01 / 09 / 2025, p. 318 / 418 3 / 46 6. Composition, according to any one of claims 1, 4 or 5, nucleic acid, according to any one of claims 2, 4 or 5, or the modified MOMP polypeptide,according to any one of claims 3 to 5, characterized in that (1) the modified MOMP polypeptide comprises a non-native loop sequence between each of the conserved domain sequences, for example, wherein the modified MOMP polypeptide comprises four non-native loop sequences and does not comprise any variable native Chlamydia sp. MOMP domain between the conserved domain sequences; and / or (2) the non-native loop sequence is between 3 and 30 amino acids in length, for example, between 4 and 20 amino acids in length.

7. Composition, according to any one of claims 1 or 4 to 6, nucleic acid, according to any one of claims 2 or 4 to 6, or modified MOMP polypeptide, according to any one of claims 3 to 6,wherein the modified MOMP polypeptide is characterized in that it comprises: (1) all five conserved domain sequences of a Chlamydia sp. MOMP polypeptide from C. trachomatis of any serovar and (2) four non-native loop sequences, wherein one non-native loop sequence is located between each of the conserved domain sequences and wherein the modified MOMP polypeptide does not comprise any native Chlamydia sp. MOMP variable domain between any of the conserved domain sequences, further wherein the non-native loop sequences are between 3 and 30 amino acids in length and are no more than 40% identical to any native Chlamydia sp. MOMP VD (VD1, VD2, VD3 or VD4) sequence of any serovar.

8. Composition, according to any one of claims 1 or 4 to 7, nucleic acid, according to any one of claims 2 or 4 to 7, or the modified MOMP polypeptide,according to any one of claims 3 to 7, characterized in that (i) a non-native handle sequence replacing VD1 comprises a sequence according to SEQ ID NO: 462 or 466 (e.g., SEQ ID NO: 462); (ii) a non-native handle sequence replacing VD2 comprises a sequence according to SEQ ID NO: 463 or 467 (e.g., SEQ ID NO: 463); (iii) a non-native handle sequence replacing VD3 comprises a sequence according to SEQ ID NOs 464 or 468 (e.g., SEQ ID NO: 464); and / or (iv) a non-native loop sequence replacing VD4 comprises a sequence according to SEQ ID NO: 465 or 469 (e.g., SEQ ID NO: 465), for example, where the modified MOMP polypeptide comprises four non-native loop sequences according to SEQ ID NOs 462, 463, 464 and 465 in place of VD1, VD2, VD3 and VD4, respectively.

9. Composition, according to any one of claims 1 or 4 to 8, nucleic acid,according to any one of claims 2 or 4 to 8, or the modified MOMP polypeptide according to any one of claims 3 to 8, characterized in that the modified MOMP polypeptide comprises a sequence according to any one of SEQ ID NOs: 486-489 (e.g., SEQ ID NO: 486) or a sequence that has at least 70% (e.g., at least 90 or 95%) identity therewith.

10. Composition, according to any one of claims 1 or 4 to 9, or nucleic acid, according to any one of claims 2 or 4 to 9, characterized in that (1) the modified MOMP polypeptide further comprises a secretion signal peptide sequence, optionally wherein the secretion signal peptide sequence comprises a secretion signal peptide sequence of the HA protein of influenza A virus, for example,wherein the secretory signal peptide sequence comprises a sequence according to SEQ ID NO: 187 or SEQ ID NO: 188; and / or (2) the nucleic acid comprises a nucleotide sequence according to any of the SEQ ID NO: 551-566 (e.g., SEQ ID NO: 551) or a sequence that has at least 50% identity therewith.

11. Composition, according to any one of claims 1 or 4 to 10, or the nucleic acid, according to any one of claims 2 or 4 to 10, characterized in that the nucleic acid is a messenger RNA (mRNA), optionally wherein (i) the mRNA comprises at least one 5' untranslated region (UTR 5'), at least one 3' untranslated region (UTR 3') and / or at least one polyadenylation sequence (poly(A)); (ii) the mRNA comprises at least one chemical modification, for example, where the chemical modification comprises N1-methylpseudouridine,optionally, wherein the chemical modification comprises N1-methylpseudouridine in place of each uridine; and / or (iii) the mRNA is a self-replicating mRNA or a non-replicating mRNA, for example, a non-replicating mRNA.

12. Composition or nucleic acid, according to Petition 870250077861, dated 01 / 09 / 2025, page 321 / 418 6 / 46 claim 11, characterized in that the mRNA comprises or consists of (for example, consists of) the following structural elements: - a 5' cap, for example, a cap with the following structure: - a 5' untranslated region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; - a protein-coding region having the nucleic acid sequence according to SEQ ID NO: 213; - an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO: 839 and - a poly(A) tail, optionally, in which the mRNA is chemically modified and in which the chemical modification comprises or consists of (e.g.,consists of) N1-methylpseudouridine in place of each uridine.

13. Composition, characterized in that it comprises (1) the nucleic acid, as defined in any one of claims 2 or 4 to 12; or (2) the polypeptide, as defined in any one of claims 3 to 9, preferably wherein the composition is an immunogenic composition.

14. Composition, according to claim 13, characterized in that it is as defined in (1) and the composition further comprises: Petition 870250077861, dated 01 / 09 / 2025, p. 322 / 418 7 / 46 (i) a nucleic acid (e.g., mRNA) comprising a nucleotide sequence encoding a chimeric variable domain (VD) polypeptide of Chlamydia sp. MOMP, wherein the chimeric VD polypeptide of MOMP comprises an amino acid sequence comprising two or more VD sequences of Chlamydia sp. MOMP from different serovars of Chlamydia sp. and / or (ii) one or more (e.g., one, two,three or four) of: (a) a nucleic acid (e.g., mRNA) comprising a nucleotide sequence encoding a Chlamydia sp. CT443 polypeptide; (b) a nucleic acid (e.g., mRNA) comprising a nucleotide sequence encoding a Chlamydia sp. CT584 polypeptide; (c) a nucleic acid (e.g., mRNA) comprising a nucleotide sequence encoding a Chlamydia sp. CT600 polypeptide; and (d) a nucleic acid (e.g., mRNA) comprising a nucleotide sequence encoding a Chlamydia sp. CT812 polypeptide, optionally, wherein the composition comprises: the nucleic acid of (i) and the nucleic acid of (ii)(a); the nucleic acid of (i) and the nucleic acid of (ii)(b); or the nucleic acid of (i), the nucleic acid of (ii)(a) and the nucleic acid of (ii)(b); for example, wherein the composition comprises the nucleic acid of (i), the nucleic acid of (ii)(a) and the nucleic acid of (ii)(b). the nucleic acid of (i),the nucleic acid of (ii)(a) and the nucleic acid of (ii)(b). Petition 870250077861, dated 01 / 09 / 2025, p. 323 / 418 8 / 46 15. Composition, according to any one of claims 1 and 14, characterized in that (A) one or more nucleic acids are an mRNA, optionally wherein (1) the mRNA comprises at least one 5' untranslated region (UTR 5'), at least one 3' untranslated region (UTR 3') and / or at least one polyadenylation sequence (poly(A)); (2) the mRNA comprises at least one chemical modification, for example, wherein the chemical modification comprises N1-methylpseudouridine, optionally wherein the chemical modification comprises N1-methylpseudouridine in place of each uridine; and / or (3) the mRNA is a self-replicating mRNA or a non-replicating mRNA, for example, a non-replicating mRNA and / or (B) the composition further comprises a lipid nanoparticle (LNP), optionally wherein the nucleic acid is encapsulated in the LNP.

16. Composition according to claim 13, characterized in that it is as defined in (2) and the composition further comprises: (i) a chimeric variable domain (VD) polypeptide of Chlamydia sp. MOMP, wherein the chimeric VD polypeptide of MOMP comprises an amino acid sequence comprising two or more VD sequences of Chlamydia sp. MOMP from different serovars of Chlamydia sp.and / or (ii) one or more (for example, one, two, three or four) of: (a) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT443 polypeptide; (b) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT584 polypeptide; (c) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT600 polypeptide; or (d) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT812 polypeptide, optionally, wherein the composition comprises the polypeptide of (i) and the polypeptide of (ii)(a); or the polypeptide of (i) and the polypeptide of (ii)(b); or the polypeptide of (i), the polypeptide of (ii)(a) and the polypeptide of (ii)(b), for example, wherein the composition comprises the polypeptide of (i), the polypeptide of (ii)(a) and the polypeptide of (ii)(b). 17.Composition, according to any one of claims 1, 4 to 12 and 14 to 16, characterized in that the chimeric VD polypeptide of MOMP comprises conserved domain sequence portions of a native Chlamydia sp. MOMP polypeptide flanking each of two or more VD sequences of MOMP, optionally wherein the conserved domain sequence portions are conserved domain sequence portions of a native Chlamydia sp. MOMP polypeptide flanking the VD in its native Chlamydia sp. MOMP polypeptide, optionally further, wherein each conserved domain sequence portion comprises between 3 and 30 amino acid residues of a conserved domain sequence of a native Chlamydia sp. MOMP polypeptide and, wherein, the between 3 and 30 amino acid residues are immediately adjacent to the VD sequence in its native Chlamydia sp. MOMP polypeptide.Composition, according to any one of claims 1, 4 to 12 and 14 to 17, characterized in that the chimeric polypeptide VD of MOMP comprises Petition 870250077861, dated 01 / 09 / 2025, p. 325 / 418 10 / 46 (1) VD sequences of MOMP from four different serovars, for example, where the different serovars are serovars D, E, F or G of C. trachomatis; (2) (i) two VD1 sequences of MOMP from different serovars of Chlamydia sp. and / or (ii) two VD2 sequences of MOMP from different serovars of Chlamydia sp. and / or (iii) a MOMP VD3 sequence and / or (iv) two MOMP VD4 sequences from different Chlamydia sp. serovars, optionally, wherein the different serovars are selected from C. trachomatis serovars D, E, F or G and / or (3) a MOMP VD sequence from C. trachomatis serovar D or E and a MOMP VD sequence from C. trachomatis serovar F or G. 19.Composition, according to any one of claims 1, 4 to 12 or 14 to 18, characterized in that the chimeric polypeptide VD of MOMP comprises at least one (for example, four) of (1)-(4): (1) a VD1 sequence of MOMP from serovar D and a VD1 sequence of MOMP from serovar F or a VD1 sequence of MOMP from serovar E and a VD1 sequence of MOMP from serovar F or G (for example, a VD1 sequence of MOMP from serovar E and a VD1 sequence of MOMP from serovar G) and / or (2) a VD2 sequence of MOMP from serovar E and a VD2 sequence of MOMP from serovar F or a VD2 sequence of MOMP from serovar D and a VD2 sequence of MOMP from serovar G (for example, a VD2 sequence of MOMP from serovar D and a VD2 sequence of MOMP from serovar G) and / or (3) a VD3 sequence of MOMP of serovar G or Petition 870250077861, dated 01 / 09 / 2025, p.326 / 418 11 / 46 a VD3 sequence of serovar F (e.g., serovar F) and / or (4) a MOMP VD4 sequence of serovar E and a MOMP VD4 sequence of serovar G or a MOMP VD4 sequence of serovar D and a MOMP VD4 sequence of serovar F (e.g., a MOMP VD4 sequence of serovar D and a MOMP VD4 sequence of serovar F), wherein serovars D, E, F, and G are of C. trachomatis.optionally, wherein the chimeric VD polypeptide of MOMP comprises: (i) a VD1 sequence of MOMP from serovar D and a VD1 sequence of MOMP from serovar F, a VD2 sequence of MOMP from serovar E and a VD2 sequence of MOMP from serovar F, a VD3 sequence of MOMP from serovar G, a VD4 sequence of MOMP from serovar E and a VD4 sequence of MOMP from serovar G; or (ii) a VD1 sequence of MOMP from serovar E and a VD1 sequence of MOMP from serovar F, a VD2 sequence of MOMP from serovar D and a VD2 sequence of MOMP from serovar G, a VD3 sequence of MOMP from serovar F, a VD4 sequence of MOMP from serovar D and a VD4 sequence of MOMP from serovar F, for example, wherein the chimeric VD polypeptide of MOMP comprises VD sequences of MOMP according to (ii). 20.Composition, according to any one of claims 1, 4 to 12 or 14 to 19, characterized in that (1) the chimeric VD polypeptide of MOMP comprises a sequence according to any one of SEQ ID NO: 490505 (for example, SEQ ID NO: 503) or a sequence that has at least 70% (for example, at least 90 or 95%) identity therewith; Petition 870250077861, dated 01 / 09 / 2025, p. 327 / 418 12 / 46 (2) the nucleic acid comprising a nucleotide sequence encoding a chimeric VD polypeptide of Chlamydia sp. comprises a nucleotide sequence corresponding to SEQ ID NO: 567-630 (e.g., SEQ ID NO: 617) or a sequence that has at least 50% identity with it; (3) the CT443 polypeptide from Chlamydia sp. comprises a sequence conforming to SEQ ID NO: 507-508 (e.g., SEQ ID NO: 507) or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it; (4) the nucleic acid comprising a nucleotide sequence encoding the CT443 polypeptide of Chlamydia sp. comprises a nucleotide sequence according to any of the SEQ ID NO: 707-710 (e.g., SEQ ID NO: 707) or a sequence that has at least 50% (e.g., at least 75%) identity with it; (5) the CT584 polypeptide from Chlamydia sp. comprises a sequence conforming to any of the SEQ ID NO: 509512 (for example, SEQ ID NO: 510) or a sequence that has at least 70% (for example, at least 90 or 95%) identity with it; (6) the nucleic acid comprising a nucleotide sequence encoding the Chlamydia sp. CT584 polypeptide comprises a nucleotide sequence according to any of the SEQ ID NO: 711-718 (e.g., SEQ ID NO: 715) or a sequence that has at least 50% (e.g., at least 75%) identity with it; (7) the CT600 polypeptide of Chlamydia sp. comprises a sequence in accordance with any of the SEQ ID NO: 513514 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity therewith; Petition 870250077861, dated 01 / 09 / 2025, p. 328 / 418 13 / 46 (8) the nucleic acid comprising a nucleotide sequence encoding the CT600 polypeptide of Chlamydia sp. comprises a nucleotide sequence according to any of the SEQ ID NO: 719-722 or a sequence that has at least 50% (e.g., at least 75%) identity therewith; (9) the Chlamydia sp. CT812 polypeptide comprises a sequence according to any one of the SEQ ID NO: 515535 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity therewith; and / or (10) the nucleic acid comprising a nucleotide sequence encoding the Chlamydia sp. CT812 polypeptide comprises a nucleotide sequence according to any one of the SEQ ID NO: 723-762 or a sequence that has at least 50% (e.g., at least 75%) identity therewith.

21. Composition according to any one of claims 1, 4 to 12, 14, 15 or 17 to 20, characterized in that (1) the nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT443 polypeptide It is an mRNA, and mRNA comprises or consists of (for example, consists of) the following structural elements: - a 5' cap, for example,a 5' cap with the following structure: - an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; Petition 870250077861, dated 01 / 09 / 2025, page 329 / 418 14 / 46 - a protein-coding region having the nucleic acid sequence according to SEQ ID NO: 369; - an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO: 839 and - a poly(A) tail; (2) the nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT584 polypeptide is an mRNA and the mRNA comprises or consists of (e.g., consists of) the following structural elements: - a 5' cap, for example,a 5' cap with the following structure: - an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; - a protein-coding region having the nucleic acid sequence according to SEQ ID NO: 377; - an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO: 839; and - a poly(A) and / or (3) tail. The nucleic acid comprising a nucleotide sequence encoding a chimeric VD polypeptide of Chlamydia sp. MOMP is an mRNA, and the mRNA comprises or consists of (for example, consists of) the following structural elements: - a 5' cap, for example, a 5' cap with the following structure: Petition 870250077861, dated 01 / 09 / 2025.pg. 330 / 418 15 / 46 O HN J***|UZ I Ό — Ρ=O ch3 II X ι O CH3 ο - an untranslated 5' region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; - a protein-coding region having the nucleic acid sequence according to SEQ ID NO: 870; - an untranslated 3' region (3' UTR) having the nucleic acid sequence according to SEQ ID NO: 839 and - a poly(A) tail.

22. Composition, according to any one of claims 1, 4 to 12, 14, 15 or 17 to 21, characterized in that it comprises: (1) the nucleic acid (e.g., mRNA), as defined in claim 10(2), wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 551 or a sequence that has at least 50% (e.g., at least 75%) identity therewith (e.g., wherein the nucleic acid is an mRNA, as defined in claim 12); the nucleic acid (e.g.,mRNA) comprises a nucleotide sequence encoding the chimeric polypeptide VD of Chlamydia sp. MOMP, wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 617 or a sequence having at least 50% (e.g., at least 75%) identity therewith (e.g., wherein the nucleic acid is mRNA, as defined in claim 21(3)) and nucleic acid (e.g., mRNA) comprises a nucleotide sequence encoding the polypeptide CT443 of Petition 870250077861, dated 01 / 09 / 2025, p. 331 / 418 16 / 46 Chlamydia sp., wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 707 or a sequence that has at least 50% (e.g., at least 75%) identity therewith (e.g., wherein the nucleic acid is mRNA, as defined in claim 21(1)); or (2) the nucleic acid (e.g., mRNA), as defined in claim 10(2),wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 551 or a sequence that has at least 50% (e.g., at least 75%) identity therewith (e.g., wherein the nucleic acid is an mRNA, as defined in claim 12); the nucleic acid (e.g., mRNA) comprises a nucleotide sequence encoding the chimeric polypeptide VD of Chlamydia sp., wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 617 or a sequence having at least 50% (e.g., at least 75%) identity therewith (e.g., wherein the nucleic acid is mRNA, as defined in claim 21(3)) and the nucleic acid (e.g., mRNA) comprises a nucleotide sequence encoding the polypeptide CT584 of Chlamydia sp., wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 715 or a sequence having at least 50% (e.g.,at least 75%) of identity with it (for example, where the nucleic acid is mRNA, as defined in claim 21(2)); or (3) nucleic acid (for example, mRNA), as defined in claim 10(2), wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 551 or a sequence having at least 50% (for example, at least 75%) of identity with it (for example, where the nucleic acid is Petition 870250077861, 01 / 09 / 2025, p. 332 / 418 17 / 46 an mRNA, as defined in claim 12); The nucleic acid (e.g., mRNA) comprises a nucleotide sequence encoding the chimeric polypeptide VD of Chlamydia sp. MOMP, wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 617 or a sequence that has at least 50% (e.g., at least 75%) identity therewith (e.g., where the nucleic acid is mRNA,as defined in claim 21(3)); the nucleic acid (e.g., mRNA) comprises a nucleotide sequence encoding the Chlamydia sp. polypeptide CT443, wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 707 or a sequence that has at least 50% (e.g., at least 75%) identity therewith (e.g., wherein the nucleic acid is mRNA, as defined in claim 21(1)) and the nucleic acid (e.g., mRNA) comprises a nucleotide sequence encoding the Chlamydia sp. polypeptide CT584, wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 715 or a sequence that has at least 50% (e.g., at least 75%) identity therewith (e.g., wherein the nucleic acid is mRNA, as defined in claim 21(2)); or (4) the nucleic acid (e.g., mRNA), as defined in claim 9,wherein the modified MOMP polypeptide comprises a sequence according to SEQ ID NO: 486 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity therewith; the nucleic acid (e.g., mRNA) comprising a nucleotide sequence encoding the chimeric VD polypeptide of Chlamydia sp. MOMP, wherein the chimeric VD polypeptide Petition 870250077861, dated 01 / 09 / 2025, p. MOMP 333 / 418 18 / 46 comprises a sequence according to SEQ ID NO: 503 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity with it and the nucleic acid (e.g., mRNA) comprising a nucleotide sequence encoding the Chlamydia sp. CT443 polypeptide, wherein the encoding of the Chlamydia sp. CT443 polypeptide comprises a sequence according to SEQ ID NO: 507 or a sequence that has at least 75% (e.g.,at least 90 or 95%) identity with it; or (5) the nucleic acid (e.g., mRNA), as defined in claim 9, wherein the modified MOMP polypeptide comprises a sequence according to SEQ ID NO: 486 or a sequence having at least 70% (e.g., at least 90 or 95%) identity with it; the nucleic acid (e.g., mRNA) comprising a nucleotide sequence encoding the chimeric VD polypeptide of Chlamydia sp. MOMP, wherein the chimeric VD polypeptide of MOMP comprises a sequence according to SEQ ID NO: 503 or a sequence having at least 75% (e.g., at least 90 or 95%) identity with it and the nucleic acid comprising a nucleotide sequence encoding the CT584 polypeptide of Chlamydia sp., wherein the CT584 polypeptide of Chlamydia sp. includes a sequence matching SEQ ID NO: 510 or a sequence that has at least 75% (for example,at least 90 or 95%) of identity therewith or (6) the nucleic acid (e.g., mRNA), as defined in claim 9, wherein the modified MOMP polypeptide comprises a sequence according to SEQ ID NO: 486 or a sequence having at least 70% (e.g., at least 90 or 95%) of identity therewith; the nucleic acid (e.g., mRNA) comprising a nucleotide sequence encoding the chimeric VD polypeptide of Chlamydia sp. MOMP, wherein the chimeric VD polypeptide of MOMP comprises a sequence according to SEQ ID NO: 503 or a sequence having at least 75% (e.g., at least 90 or 95%) of identity therewith; the nucleic acid (e.g., mRNA) comprising a nucleotide sequence encoding the CT443 polypeptide of Chlamydia sp.,wherein the encoding of the Chlamydia sp. CT443 polypeptide comprises a sequence according to SEQ ID NO: 507 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity therewith; and the nucleic acid comprising a nucleotide sequence encoding the Chlamydia sp. CT584 polypeptide, wherein the Chlamydia sp. CT584 polypeptide comprises a sequence according to SEQ ID NO: 510 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity therewith, for example, wherein the composition comprises the nucleic acids as defined in (3) or the nucleic acids as defined in (6).

23. Composition, according to any one of claims 16 to 20, characterized in that it comprises: (1) the modified MOMP polypeptide comprising a sequence according to SEQ ID NO: 486 or a sequence that has at least 70% (for example,at least 90 or 95%) identity with it; the chimeric polypeptide VD of Chlamydia sp. MOMP comprising a sequence according to SEQ ID NO: 503 or Petition 870250077861, dated 01 / 09 / 2025, p. 335 / 418 20 / 46, a sequence that has at least 75% (e.g., at least 90 or 95%) identity with it; and the polypeptide CT443 of Chlamydia sp. comprising a sequence according to SEQ ID NO: 507 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity with it; or (2) the modified MOMP polypeptide comprising a sequence according to SEQ ID NO: 486 or a sequence having at least 70% (e.g., at least 90 or 95%) identity with it; the chimeric VD polypeptide of Chlamydia sp. MOMP comprising a sequence according to SEQ ID NO: 503 or a sequence having at least 75% (e.g.,at least 90 or 95%) identity with it and the Chlamydia sp. CT584 polypeptide comprising a sequence according to SEQ ID NO: 510 or a sequence having at least 75% (e.g., at least 90 or 95%) identity with it; or (3) the modified MOMP polypeptide comprising a sequence according to SEQ ID NO: 486 or a sequence having at least 70% (e.g., at least 90 or 95%) identity with it; the chimeric VD polypeptide of Chlamydia sp. MOMP comprising a sequence according to SEQ ID NO: 503 or a sequence having at least 75% (e.g., at least 90 or 95%) identity with it; the Chlamydia sp. CT443 polypeptide. comprising a sequence corresponding to SEQ ID NO: 507 or a sequence that has at least 75% (for example, at least 90 or 95%) identity with the same and Petition 870250077861, dated 01 / 09 / 2025,pg. 336 / 418 21 / 46 the Chlamydia sp. CT584 polypeptide comprising a sequence according to SEQ ID NO: 510 or a sequence that has at least 75% (for example, at least 90 or 95%) identity therewith, for example, wherein the composition comprises the polypeptides as defined in (3).

24. Combination, characterized in that it comprises a nucleic acid, as defined in any one of claims 2 or 4 to 12, and: (i) a nucleic acid comprising a nucleotide sequence encoding a chimeric variable domain (VD) polypeptide of Chlamydia sp. MOMP, wherein the chimeric VD polypeptide of MOMP comprises an amino acid sequence comprising two or more VD sequences of Chlamydia sp. MOMP from different serovars of Chlamydia sp. and / or (ii) one or more (for example, one, two,three or four) of: (a) a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT443 polypeptide; (b) a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT584 polypeptide; (c) a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT600 polypeptide; or (d) a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT812 polypeptide; optionally, wherein the combination comprises Petition 870250077861, dated 01 / 09 / 2025, page 337 / 418 22 / 46 the nucleic acid of (i) and the nucleic acid of (ii)(a); the nucleic acid of (i) and the nucleic acid of (ii)(b); or the nucleic acid of (i), the nucleic acid of (ii)(a) and the nucleic acid of (ii)(b), for example, wherein the combination comprises the nucleic acid of (i), the nucleic acid of (ii)(a) and the nucleic acid of (ii)(b), optionally wherein the nucleic acids are,as defined in claim 22, optionally further wherein the nucleic acids are present in the same composition (e.g., in the same composition).

25. Combination, characterized in that it comprises the polypeptide, as defined in any of claims 3 to 9, and: (i) a chimeric variable domain (VD) polypeptide of Chlamydia sp. MOMP, wherein the chimeric VD polypeptide of MOMP comprises an amino acid sequence comprising two or more VD sequences of Chlamydia sp. MOMP from different serovars of Chlamydia sp. and / or (ii) one or more (e.g., one, two,three or four) of: (a) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT443 polypeptide; (b) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT584 polypeptide; (c) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT600 polypeptide; or (d) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT812 polypeptide, optionally, wherein the combination comprises Petition 870250077861, dated 01 / 09 / 2025, page 338 / 418 23 / 46 the polypeptide of (i) and the polypeptide of (ii)(a); the polypeptide of (i) and the polypeptide of (ii)(b); or the polypeptide of (i), the polypeptide of (ii)(a) and the polypeptide of (ii)(b), for example, wherein the combination comprises the polypeptide of (i), the polypeptide of (ii)(a) and the polypeptide of (ii)(b). optionally wherein the polypeptides are, as defined in claim 23,optionally, polypeptides are present in the same composition or in two or more separate compositions (e.g., in the same composition).

26. Nucleic acid, characterized in that it comprises a nucleotide sequence encoding a chimeric variable domain (VD) polypeptide of Chlamydia sp. MOMP, wherein the chimeric VD polypeptide of MOMP comprises an amino acid sequence comprising two or more VD sequences of Chlamydia sp. MOMP from different serovars of Chlamydia sp., optionally wherein the Chlamydia sp. is Chlamydia trachomatis.

27. Chimeric variable domain (VD) polypeptide of Chlamydia sp. MOMP, characterized in that it comprises an amino acid sequence comprising two or more VD sequences of Chlamydia sp. MOMP from different serovars of Chlamydia sp., optionally wherein the Chlamydia sp. is Chlamydia trachomatis.

28. Nucleic acid according to claim 26,or the chimeric VD polypeptide of MOMP, according to claim 27, characterized in that (a) the chimeric VD polypeptide of MOMP comprises conserved domain sequence portions of a native Chlamydia sp. MOMP polypeptide flanking each of two or more VD sequences of MOMP; (b) the chimeric VD polypeptide of MOMP comprises VD sequences of MOMP from four different serovars, optionally wherein the different serovars are selected from serovars D, E, F or G of C. trachomatis.

29. Nucleic acid, according to claim 26 or 28, or the chimeric VD polypeptide of MOMP, according to claim 27 or 28,characterized in that the chimeric polypeptide VD of MOMP comprises: (1) (i) two VD1 sequences of MOMP from different serovars of Chlamydia sp. and / or (ii) two VD2 sequences of MOMP from different serovars of Chlamydia sp. and / or (iii) one VD3 sequence of MOMP and / or (iv) two VD4 sequences of MOMP from different serovars of Chlamydia sp., optionally, wherein the different serovars are selected from serovars D, E, F or G of C. trachomatis and / or (2) one VD sequence of MOMP from serovar D or E of C. trachomatis and one VD sequence of MOMP from serovar F or G of C. trachomatis.

30. Nucleic acid, according to claim 29, or the chimeric polypeptide VD of MOMP, according to claim 29, characterized in that the chimeric polypeptide VD of MOMP comprises at least one (for example,four) of (i)(iv): (i) a VD1 sequence of MOMP from serovar D and a VD1 sequence of MOMP from serovar F or a VD1 sequence of MOMP from serovar E and a VD1 sequence of MOMP from serovar F or G (for example, a VD1 sequence of MOMP from serovar E and a VD1 sequence of MOMP from serovar G) and / or (ii) a VD2 sequence of MOMP from serovar E and a VD2 sequence of MOMP from serovar F or a VD2 sequence of MOMP from serovar D and a VD2 sequence of MOMP from serovar G (for example, a VD2 sequence of MOMP from serovar D and a VD2 sequence of MOMP from serovar G) and / or (iii) a VD3 sequence of MOMP from serovar G or a VD3 sequence from serovar F (e.g., serovar F) and / or (iv) a VD4 MOMP sequence from serovar E and a VD4 MOMP sequence from serovar G or a VD4 MOMP sequence from serovar D and a VD4 MOMP sequence from serovar F (e.g., a VD4 MOMP sequence from serovar D and a VD4 MOMP sequence from serovar F),wherein serovars D, E, F or G are of C. trachomatis, optionally, wherein the chimeric polypeptide VD of MOMP comprises: (1) a VD1 sequence of MOMP from serovar D and a VD1 sequence of MOMP from serovar F, a VD2 sequence of MOMP from serovar E and a VD2 sequence of MOMP from serovar F, a VD3 sequence of MOMP from serovar G, a VD4 sequence of MOMP from serovar E and a VD4 sequence of MOMP from serovar G; or (2) a MOMP VD1 sequence from serovar E and a MOMP VD1 sequence from serovar F, a MOMP VD2 sequence from serovar D and a MOMP VD2 sequence from serovar G, a MOMP VD3 sequence from serovar F, a MOMP VD4 sequence from serovar D and a MOMP VD4 sequence from serovar F, wherein serovars D, E, F or G are from C. trachomatis, for example, wherein the chimeric MOMP VD polypeptide comprises MOMP VD sequences according to (2). Petition 870250077861, dated 01 / 09 / 2025, p. 341 / 418 26 / 46 31. Nucleic acid, according to any one of claims 28 to 30,or the chimeric VD polypeptide of MOMP, according to any one of claims 28 to 30, characterized in that (a) the conserved domain sequence portions are conserved domain sequence portions of a Chlamydia sp. native MOMP polypeptide that flanks the VD in its Chlamydia sp. native MOMP polypeptide and / or (b) each conserved domain sequence portion comprises between 3 and 30 amino acid residues of a conserved domain sequence of a Chlamydia sp. native MOMP polypeptide, wherein the between 3 and 30 amino acid residues are immediately adjacent to the VD sequence in its Chlamydia sp. native MOMP polypeptide.

32. Nucleic acid, according to any one of claims 26 or 28 to 31, or chimeric VD polypeptide of MOMP, according to any one of claims 27 to 31,characterized in that the chimeric polypeptide VD of MOMP comprises a sequence according to any of the SEQ ID NO: 490505 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it, for example, wherein the chimeric polypeptide MOVD comprises a sequence according to SEQ ID NO: 503 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it.

33. Nucleic acid, according to any one of claims 26 or 28 to 32, characterized in that the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 567-630 or a sequence that has at least 50% (for example, at least 75%) identity therewith, for example, in which the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 617 or a sequence that has at least 50% (for example, at least 75%) identity therewith.at least 75%) of identity with it.

34. Nucleic acid, according to any one of claims 26 or 28 to 33, characterized in that it is a messenger RNA (mRNA), optionally wherein (i) the mRNA comprises at least one 5' untranslated region (UTR 5'), at least one 3' untranslated region (UTR 3') and / or at least one polyadenylation sequence (poly(A)); (ii) the mRNA comprises at least one chemical modification, for example, wherein the chemical modification comprises N1-methylpseudouridine, optionally wherein the chemical modification comprises N1-methylpseudouridine in place of each uridine; and / or (iii) the mRNA is a self-replicating mRNA or a non-replicating mRNA, for example, a non-replicating mRNA.

35. Nucleic acid, according to any one of claims 26 or 28 to 34, characterized in that the mRNA comprises or consists of (for example, consists of) the following structural elements: - a 5' cap, for example,a 5' cap with the following structure: - a 5' untranslated region (5' UTR) having the nucleic acid sequence according to SEQ ID NO: 838; - a protein-coding region having the nucleic acid sequence according to SEQ ID NO: 870; - a 3' untranslated region (3' UTR) having the nucleic acid sequence according to SEQ ID NO: 839; and - a poly(A) tail, optionally, in which the mRNA is chemically modified and in which the chemical modification comprises or consists of (for example, consists of) N1-methylpseudouridine in place of each uridine.

36. Composition, characterized in that it comprises nucleic acid, as defined in any one of claims 26 or 28 to 35, preferably wherein the composition is an immunogenic composition.

37. Composition, characterized in that it comprises the chimeric polypeptide VD of MOMP, as defined in any one of claims 27 to 32,preferably wherein the composition is an immunogenic composition, for example, wherein the composition comprises an adjuvant.

38. Composition according to claim 36, characterized in that the composition further comprises: (i) a nucleic acid comprising a nucleotide sequence encoding a modified MOMP polypeptide, wherein the modified MOMP polypeptide has an amino acid sequence comprising two or more conserved domain sequences of a native Chlamydia sp. MOMP polypeptide and a non-native loop sequence between the conserved domain sequences; and / or (ii) one or more (for example, one, two, three or four) of: (a) a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT443 polypeptide; Petition 870250077861, dated 01 / 09 / 2025,p. 344 / 418 29 / 46 (b) a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT584 polypeptide; (c) a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT600 polypeptide or (d) a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT812 polypeptide; optionally, wherein the composition comprises the nucleic acid of (i) and the nucleic acid of (ii)(a); the nucleic acid of (i) and the nucleic acid of (ii)(b); or the nucleic acid of (i), the nucleic acid of (ii)(a) and the nucleic acid of (ii)(b), for example, wherein the composition comprises the nucleic acid of (i), the nucleic acid of (ii)(a) and the nucleic acid of (ii)(b).

39. Composition according to claim 38, characterized in that one or more nucleic acids are an mRNA, optionally wherein (i) the mRNA comprises at least one 5' untranslated region (5' UTR),at least one 3' untranslated region (UTR 3') and / or at least one polyadenylation sequence (poly(A)); (ii) the mRNA comprises at least one chemical modification, for example, wherein the chemical modification comprises N1-methylpseudouridine, optionally wherein the chemical modification comprises N1-methylpseudouridine in place of each uridine; and / or (iii) the mRNA is a self-replicating mRNA or a non-replicating mRNA, for example, a non-replicating mRNA.

40. Composition according to claim 38 or Petition 870250077861, dated 01 / 09 / 2025, p. 345 / 418 30 / 46 39, characterized in that: (1) the nucleic acid comprising a nucleotide sequence encoding the modified MOMP polypeptide is as defined in any one of claims 2 or 4 to 12, and / or (2) any one of the nucleic acids comprising a nucleotide sequence encoding the CT443 polypeptide from Chlamydia sp.,the nucleic acid comprising a nucleotide sequence encoding the CT584 polypeptide of Chlamydia sp., the nucleic acid comprising a nucleotide sequence encoding the CT600 polypeptide of Chlamydia sp. or the nucleic acid comprising a nucleotide sequence encoding the CT812 polypeptide of Chlamydia sp. is as defined in any one of claims 20 to 22.

41. Composition according to any one of claims 38 to 40, characterized in that it comprises: (1) the nucleic acid (e.g., mRNA), as defined in claim 10(2), wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 551 or a sequence having at least 50% (e.g., at least 75%) identity therewith (e.g., wherein the nucleic acid is an mRNA, as defined in claim 12); the nucleic acid (e.g., mRNA), as defined in claim 33,wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 617 or a sequence that has at least 50% (e.g., at least 75%) identity therewith (e.g., wherein the nucleic acid is mRNA, as defined in claim 35) and the nucleic acid (e.g., mRNA) comprises a nucleotide sequence encoding the CT443 polypeptide of Chlamydia sp., wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 707 or a sequence that has at least 50% (e.g., at least 75%) identity therewith (e.g., wherein the nucleic acid is mRNA, as defined in claim 21(1)); or (2) the nucleic acid (e.g., mRNA), as defined in claim 10(2), wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 551 or a sequence having at least 50% (e.g.,at least 75%) of identity with it (for example, where the nucleic acid is mRNA, as defined in claim 12); the nucleic acid (for example, mRNA), as defined in claim 33, wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 617 or a sequence having at least 50% (for example, at least 75%) identity with it (for example, wherein the nucleic acid is mRNA, as defined in claim 35) and the nucleic acid (for example, mRNA) comprises a nucleotide sequence encoding the Chlamydia sp. polypeptide CT584, wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 715 or a sequence having at least 50% (for example, at least 75%) identity with it (for example, wherein the nucleic acid is mRNA, as defined in claim 21(2)); or (3) the nucleic acid (e.g., mRNA), as defined in claim 10(2),wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 551 or a sequence that has at least 50% (e.g., at least 75%) identity therewith (e.g., wherein the nucleic acid is mRNA, as defined in claim 12); the nucleic acid (e.g., mRNA), as defined in Petition 870250077861, dated 01 / 09 / 2025, p. 347 / 418 32 / 46 claim 33, wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 617 or a sequence that has at least 50% (e.g., at least 75%) identity therewith (e.g., wherein the nucleic acid is mRNA, as defined in claim 35); The nucleic acid (e.g., mRNA) comprises a nucleotide sequence encoding the Chlamydia sp. CT443 polypeptide, wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 707 or a sequence that has at least 50% (e.g.,at least 75%) identity therewith (for example, wherein the nucleic acid is mRNA, as defined in claim 21(1)) and the nucleic acid (for example, mRNA) comprises a nucleotide sequence encoding the Chlamydia sp. CT584 polypeptide, wherein the nucleic acid comprises a nucleotide sequence according to SEQ ID NO: 715 or a sequence having at least 50% (for example, at least 75%) identity therewith (for example, wherein the nucleic acid is mRNA, as defined in claim 21(2)); or (4) the nucleic acid (for example, mRNA), as defined in claim 9, wherein the modified MOMP polypeptide comprises a sequence according to SEQ ID NO: 486 or a sequence having at least 70% (for example, at least 90 or 95%) identity therewith; the nucleic acid (for example, mRNA), as defined in claim 32,wherein the chimeric polypeptide VD of MOMP comprises a sequence according to SEQ ID NO: 503 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity with the same and the nucleic acid (e.g., mRNA) comprising Petition 870250077861, dated 01 / 09 / 2025, p. 348 / 418 33 / 46 a nucleotide sequence encoding the Chlamydia sp. polypeptide CT443, wherein the Chlamydia sp. polypeptide CT443 comprises a sequence according to SEQ ID NO: 507 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity with it or (5) the nucleic acid (e.g., mRNA), as defined in claim 9, wherein the modified MOMP polypeptide comprises a sequence according to SEQ ID NO: 486 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity with it; the nucleic acid (e.g., mRNA), as defined in claim 32,wherein the chimeric VD polypeptide of MOMP comprises a sequence according to SEQ ID NO: 503 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity therewith and the nucleic acid comprising a nucleotide sequence encoding the Chlamydia sp. CT584 polypeptide, wherein the Chlamydia sp. CT584 polypeptide comprises a sequence according to SEQ ID NO: 510 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity therewith or (6) the nucleic acid (e.g., mRNA), as defined in claim 9, wherein the modified MOMP polypeptide comprises a sequence according to SEQ ID NO: 486 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity therewith; the nucleic acid (e.g., mRNA), as defined in claim 32,wherein the chimeric polypeptide VD of MOMP comprises a sequence according to SEQ ID NO: 503 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity therewith; the nucleic acid (e.g., mRNA) comprising a nucleotide sequence encoding the Chlamydia sp. polypeptide CT443, wherein the Chlamydia sp. polypeptide CT443 comprises a sequence according to SEQ ID NO: 507 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity with it, and the nucleic acid comprising a nucleotide sequence encoding the Chlamydia sp. polypeptide CT584, wherein the Chlamydia sp. polypeptide CT584 comprises a sequence according to SEQ ID NO: 510 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity with it, for example,wherein the composition comprises nucleic acids as defined in (3) or nucleic acids as defined in (6).

42. Composition according to claim 37, characterized in that the composition further comprises: (i) a modified MOMP polypeptide, wherein the modified MOMP polypeptide has an amino acid sequence comprising two or more conserved domain sequences of a native Chlamydia sp. MOMP polypeptide and a non-native loop sequence between the conserved domain sequences; and / or (ii) one or more (for example, one, two, three or four) of: (a) a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT443 polypeptide; (b) a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT584 polypeptide; (c) a polypeptide comprising a sequence of Petition 870250077861, dated 01 / 09 / 2025,p. 350 / 418 35 / 46 amino acids of a Chlamydia sp. CT600 polypeptide or (d) a polypeptide comprising an amino acid sequence of a Chlamydia sp. CT812 polypeptide, optionally, wherein the composition comprises: the polypeptide of (i) and the polypeptide of (ii)(a); or the polypeptide of (i) and the polypeptide of (ii)(b); or the polypeptide of (i), the polypeptide of (ii)(a) and the polypeptide of (ii)(b), for example, wherein the composition comprises the polypeptide of (i), the polypeptide of (ii)(a) and the polypeptide of (ii)(b).

43. Composition according to claim 42, characterized in that (1) the modified MOMP polypeptide is as defined in any one of claims 3 to 9, and / or (2) any one of Chlamydia sp. polypeptide CT443, Chlamydia sp. polypeptide CT584, Chlamydia sp. polypeptide CT600 or Chlamydia sp. polypeptide CT812 is as defined in claim 20 or 22.

44. Composition according to claim 42 or 43,characterized in that it comprises: (1) the modified MOMP polypeptide comprising a sequence according to SEQ ID NO: 486 or a sequence that has at least 70% (e.g., at least 90 or 95%) identity therewith; the chimeric VD polypeptide of Chlamydia sp. MOMP comprising a sequence according to SEQ ID NO: 503 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity therewith; and the Chlamydia sp. CT443 polypeptide comprising a sequence according to SEQ ID NO: 507 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity therewith; or (2) the modified MOMP polypeptide comprising a sequence according to SEQ ID NO: 486 or a sequence having at least 70% (for example,at least 90 or 95%) identity with it; the chimeric polypeptide VD of Chlamydia sp. MOMP comprising a sequence according to SEQ ID NO: 503 or a sequence having at least 75% (e.g., at least 90 or 95%) identity with it and the polypeptide CT584 of Chlamydia sp. comprising a sequence according to SEQ ID NO: 510 or a sequence having at least 75% (e.g., at least 90 or 95%) identity with it or (3) the modified MOMP polypeptide comprising a sequence according to SEQ ID NO: 486 or a sequence having at least 70% (e.g., at least 90 or 95%) identity with it; the chimeric polypeptide VD of Chlamydia sp. MOMP comprising a sequence matching SEQ ID NO: 503 or a sequence that has at least 75% (for example,at least 90 or 95%) identity with the same; the Chlamydia sp. polypeptide CT443 comprising a sequence according to SEQ ID NO: 507 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity with the same, and the Chlamydia sp. polypeptide CT584 comprising a sequence according to SEQ ID NO: 510 or a sequence that has at least 75% (e.g., at least 90 or 95%) identity with the same, Petition 870250077861, dated 01 / 09 / 2025, p. 352 / 418 37 / 46 for example, wherein the composition comprises the polypeptides as defined in (3).

45. Combination, characterized in that it comprises a nucleic acid, as defined in any one of claims 26 or 28 to 35, and: (i) a nucleic acid comprising a nucleotide sequence encoding a modified MOMP polypeptide,wherein the modified MOMP polypeptide has an amino acid sequence comprising two or more conserved domain sequences of a native Chlamydia sp. MOMP polypeptide and a non-native loop sequence between the conserved domain sequences; and / or (ii) one or more (e.g., one, two, three or four) of: (a) a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT443 polypeptide; (b) a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT584 polypeptide; (c) a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT600 polypeptide; or (d) a nucleic acid comprising a nucleotide sequence encoding a Chlamydia sp. CT812 polypeptide; optionally, wherein the combination comprises the nucleic acid of (i) and the nucleic acid of (ii)(a); the nucleic acid of (i) and the nucleic acid of (ii)(b); or the nucleic acid of (i),the nucleic acid of (ii)(a) and the nucleic acid of (ii)(b), for example, wherein the combination comprises the nucleic acid of (i), the nucleic acid of (ii)(a) and the nucleic acid of (ii)(b), optionally wherein the nucleic acids are, as defined in claim 41, further optionally wherein the nucleic acids are present in the same composition (e.g., in the same composition).

46. Combination, characterized in that it comprises a polypeptide, as defined in any one of claims 27 to 32, and: (i) a modified MOMP polypeptide, wherein the modified MOMP polypeptide has an amino acid sequence comprising two or more conserved domain sequences of a native Chlamydia sp. MOMP polypeptide. and a non-native loop sequence between the conserved domain sequences; and / or (ii) one or more (e.g., one, two,three or four) of: (a) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT443 polypeptide; (b) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT584 polypeptide; (c) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT600 polypeptide; or (d) a polypeptide comprising the amino acid sequence of a Chlamydia sp. CT812 polypeptide, optionally, wherein the combination comprises the polypeptide of (i) and the polypeptide of (ii)(a); the polypeptide of (i) and the polypeptide of (ii)(b); or the polypeptide of (i), the polypeptide of (ii)(a) and the polypeptide of (i)(b). Petition 870250077861, dated 01 / 09 / 2025, page. 354 / 418 39 / 46 deo de (ii)(b), for example, wherein the combination comprises polypeptide (i), polypeptide (ii)(a) and polypeptide (ii)(b). optionally wherein the polypeptides are, as defined in claim 44,optionally, the polypeptides are present in the same composition or in two or more separate compositions.

47. Nucleic acid, according to any one of claims 2, 4 to 12, 26 or 28 to 35, composition, according to any one of claims 1, 4 to 12, 13 to 15, 17 to 23, 36 to 41, or combination, according to any one of claims 24 and 45, characterized in that: (i) the modified MOMP polypeptide further comprises a secretion signal peptide sequence; (ii) the chimeric VD polypeptide of MOMP comprises a secretion signal peptide sequence; and / or (iii) the Chlamydia sp. polypeptide CT443, the Chlamydia sp. polypeptide CT584, the Chlamydia sp. polypeptide CT600 and the Chlamydia sp. polypeptide CT812 comprise a secretion signal peptide sequence, optionally wherein the secretion signal peptide sequence is a viral secretion signal peptide sequence,optionally selected from the group consisting of: an influenza hemagglutinin (HA) secretion signal peptide sequence, a SARS-CoV-2 spike secretion signal peptide sequence, a VZV gB secretion signal peptide sequence, a VZV gE secretion signal peptide sequence, a VZV gI secretion signal peptide sequence, a VZV gK secretion signal peptide sequence, a Petition 870250077861, dated 01 / 09 / 2025, page. 355 / 418 40 / 46 secretion of measles F protein, a rubella E1 protein secretion signal peptide sequence, a rubella E2 protein secretion signal peptide sequence, a mumps F protein secretion signal peptide sequence, an Ebola GP protein secretion signal peptide sequence, and a smallpox 6kDa IC protein secretion signal peptide sequence.optionally wherein the secretion signal peptide sequence comprises an amino acid sequence according to one of the SEQ ID NOs in Table 2 or Table 2.1, for example, wherein the secretion signal peptide sequence comprises a secretion signal peptide sequence of the HA protein of influenza A virus, for example, wherein the secretion signal peptide sequence comprises a sequence according to SEQ ID NO: 187 or SEQ ID NO:

188.

48. Nucleic acid, according to any one of claims 2, 4 to 12, 26, 28 to 35 and 47, modified MOMP polypeptide, according to any one of claims 3 to 9, the chimeric VD polypeptide of MOMP, according to any one of claims 27 to 32, composition, according to any one of claims 1, 4 to 23, 36 to 44 and 47, or combination, according to any one of claims 24, 25 and 45 to 47,characterized in that: (i) the modified MOMP polypeptide comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in a conserved domain sequence of a native Chlamydia sp. MOMP polypeptide, optionally wherein the single amino acid substitution is a cysteine-to-serine substitution; (ii) the chimeric VD MOMP polypeptide comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in a conserved domain sequence of a native Chlamydia sp. MOMP polypeptide, optionally wherein the single amino acid substitution is a cysteine-to-serine substitution; and / or (iii) one or more of the Chlamydia sp. CT443 polypeptide, the Chlamydia sp. CT584 polypeptide,The Chlamydia sp. polypeptide CT600 and the Chlamydia sp. polypeptide CT812 comprise a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine ​​residue in the respective native Chlamydia sp. polypeptide, optionally where the single amino acid substitution is a cysteine ​​substitution for serine.

49. Nucleic acid, according to any one of claims 2, 4 to 12, 26, 28 to 35, 47 or 48, modified MOMP polypeptide, according to any one of claims 3 to 9 or 48, chimeric VD polypeptide of MOMP, according to any one of claims 27 to 32 or 48, composition, according to any one of claims 1, 4 to 23, 36 to 44, 47 or 48, or combination, according to any one of claims 24, 25 or 45 to 48, characterized in that (i) the modified MOMP polypeptide comprises a mutation at one or more (e.g., all) positions corresponding to a glycosylation site,(i) optionally an N-glycosylation site, in a native Chlamydia sp. MOMP polypeptide, optionally wherein the mutation is a single amino acid substitution; (ii) the chimeric VD polypeptide of MOMP comprises a mutation at one or more (e.g., all) positions corresponding to a glycosylation site, optionally an N-glycosylation site, in a native Chlamydia sp. MOMP polypeptide, op Petition 870250077861, dated 01 / 09 / 2025, p. 357 / 418 42 / 46 specifically where the mutation is a single amino acid substitution, for example, where the chimeric polypeptide VD of MOMP comprises a single amino acid substitution in each of the amino acid residues corresponding to position 9 of SEQ ID NO: 9 (e.g., substitution of N for A), position 11 of SEQ ID NO: 17 (e.g., substitution of T for A), position 17 of SEQ ID NO: 6 (e.g., substitution of S for A), positions 4 and 21 of SEQ ID NO: 18 (e.g., substitutions of N for A and S for A,respectively), position 14 of SEQ ID NO: 8 (e.g., a T to A substitution) and position 14 in SEQ ID NO: 16 (e.g., a T to A substitution); and / or (iii) one or more of the Chlamydia sp. polypeptide CT443, the Chlamydia sp. polypeptide CT584, the Chlamydia sp. polypeptide CT600, and the Chlamydia sp. polypeptide CT812 comprise a mutation at one or more (e.g., all) positions corresponding to an N-glycosylation site in the respective native Chlamydia sp. polypeptide, optionally wherein the mutation is a single amino acid substitution, e.g., wherein the Chlamydia sp. polypeptide CT584 comprises a single amino acid substitution at a position corresponding to residue 11 of SEQ ID NO: 509 (e.g., an N to Q substitution).

50. Composition according to any one of claims 1, 4 to 23, 36 to 44 or 47 to 49, or combination according to any one of claims 24, 25 or 45 to 49,characterized by the fact that one or more of the Chlamydia sp. CT443 polypeptide, the Chlamydia sp. CT584 polypeptide, the Chlamydia sp. CT600 polypeptide, and the Chlamydia sp. CT812 polypeptide comprise a heterologous transmembrane domain, optionally wherein the transmembrane domain sequence is selected from the group consisting of: a transmembrane domain sequence of the Petition 870250077861, dated 01 / 09 / 2025, page. 358 / 418 43 / 46 influenza magnulin (HA), a transmembrane domain sequence of the SARS-CoV-2 spike protein, a gB transmembrane domain sequence of VZV, a gE transmembrane domain sequence of VZV, a gI transmembrane domain sequence of VZV, a gK transmembrane domain sequence of VZV, a transmembrane domain sequence of the F protein of measles, a transmembrane domain sequence of the E1 protein of rubella, a transmembrane domain sequence of the E2 protein of rubella,A transmembrane domain sequence of the F protein from mumps and a transmembrane domain sequence of the GP protein from Ebola, optionally wherein the transmembrane domain comprises an amino acid sequence according to one of the SEQ ID NOs in Table 3, for example, wherein the transmembrane domain comprises the sequence of a transmembrane domain of the HA protein from influenza A virus, optionally wherein the transmembrane domain comprises a sequence according to SEQ ID NO: 813 or SEQ ID NO:

814.

51. Composition, according to any one of claims 1, 4 to 15, 17 to 23, 36 to 41, characterized in that it further comprises a lipid nanoparticle (LNP), optionally wherein the nucleic acid is encapsulated in the LNP.

52. Composition according to claim 51 characterized in that the LNP comprises at least one cationic lipid, optionally wherein: (i) the cationic lipid is selected from the group consisting of OF-O2, cKK-E10, OF-Deg-Lin,GL-HEPES-E3-E10-DS-3E18-1, GL-HEPES-E3-E12-DS-4-E10, GL-HEPES-E3-E12-DS-3-E14, SM-102, ALC-0315, ATX-126 and IM-001 (for example, GL-HEPES-E3E12-DS-4-E10 or IM-001); and / or (ii) the LNP further comprises a lipid conjugated with Petition 870250077861, dated 01 / 09 / 2025, page. 359 / 418 44 / 46 polyethylene glycol (PEG) (PEGylated), a cholesterol-based lipid and an auxiliary lipid, optionally wherein the lipid (PEGylated) is DMG-PEG2000 or ALC-0159 (e.g., DMG-PEG2000); the cholesterol-based lipid is cholesterol; and / or the auxiliary lipid is DOPE or DSPC.

53. Composition according to claim 51 or 52, characterized in that the LNP comprises: (i) OF-02 in a molar ratio of 40%, DMG-PEG2000 in a molar ratio of 1.5%, cholesterol in a molar ratio of 28.5% and DOPE in a molar ratio of 30%; (ii) cKK-E10 at a molar ratio of 40%, DMG-PEG2000 at a molar ratio of 1.5%, cholesterol at a molar ratio of 28,(iii) GL-HEPES-E3-E10-DS-3-E18-1 in a molar ratio of 40%, DMG-PEG2000 in a molar ratio of 1.5%, cholesterol in a molar ratio of 28.5% and DOPE in a molar ratio of 30%; (iv) GL-HEPES-E3-E12-DS-4-E10 in a molar ratio of 40%, DMG-PEG2000 in a molar ratio of 1.5%, cholesterol in a molar ratio of 28.5% and DOPE in a molar ratio of 30%; (v) GL-HEPES-E3-E12-DS-3-E14 in a molar ratio of 40%, DMG-PEG2000 in a molar ratio of 1.5%, cholesterol in a molar ratio of 28.5% and DOPE in a molar ratio of 30%; (vi) DLin-MC3-DMA (MC3) in a molar ratio of 50%, DMG-PEG2000 in a molar ratio of 1.5%, cholesterol in a molar ratio of 38.5% and DSPC in a molar ratio of 10%; (vii) IM-001 in a molar ratio of 40%, DMG-PEG2000 in a molar ratio of 1.5%, cholesterol in a molar ratio of 28.5% and DOPE in a molar ratio of 30%; (viii) SM-102 in a molar ratio of 50%, DMG Petition 870250077861, dated 01 / 09 / 2025,pg. 360 / 418 45 / 46 PEG2000 at a molar ratio of 1.5%, cholesterol at a molar ratio of 38.5% and DSPC at a molar ratio of 10%; (ix) ALC-0315 at a molar ratio of 46.3%, ALC-0159 at a molar ratio of 1.6%, cholesterol at a molar ratio of 42.7% and DSPC at a molar ratio of 9.4%; (x) ALC-0315 at a molar ratio of 47.4%, ALC-0159 at a molar ratio of 1.7%, cholesterol at a molar ratio of 40.9% and DSPC at a molar ratio of 10%; or (xi) ATX-126 at a molar ratio of 50%; DMG-PEG2000 in a molar ratio of 1.5%, cholesterol in a molar ratio of 38.5% and DOPE in a molar ratio of 10%. For example, wherein the LNP is as defined in (i), (ii), (iv) or (vii), for example, wherein the LNP is as defined in (iv) or (vii).

54. Nucleic acid, according to any one of claims 2, 4 to 12, 26, 28 to 35 or 47 to 49, modified MOMP polypeptide, according to any one of claims 3 to 9, 48 or 49, chimeric VD polypeptide of MOMP,according to any one of claims 27 to 32, 48 or 49, the composition, according to any one of claims 1, 4 to 23, 36 to 44 or 47 to 53, or combination, according to any one of claims 24, 25 or 45 to 50, characterized in that it is for use as a medicament.

55. Nucleic acid, according to any one of claims 2, 4 to 12, 26, 28 to 35 or 47 to 49, modified MOMP polypeptide, according to any one of claims 3 to 9, 48 or 49, chimeric VD polypeptide of MOMP, according to any one of claims 27 to 32, 48 or 49, composition, according to any one of claims 1, 4 to 23, 36 to 44 and 47 to 53, or combination, according to any one of claims 24, 25 or 45 to 50, characterized in that it is for use in the treatment or Petition 870250077861, dated 01 / 09 / 2025, page. 361 / 418 46 / 46 prevention of a Chlamydia sp. infection, preferably where the infection is a C. trachomatis infection,For example, a genital infection caused by C. trachomatis.

56. Vaccine, characterized in that it comprises the nucleic acid, as defined in any one of claims 2, 4 to 12, 26, 28 to 35 or 47 to 49, the modified MOMP polypeptide, as defined in any one of claims 3 to 9, 48 or 49, the chimeric VD polypeptide of MOMP, as defined in any one of claims 27 to 32, 48 or 49, the composition, as defined in any one of claims 1, 4 to 23, 36 to 44 or 47 to 53, or the combination, as defined in any one of claims 24, 25 or 45 to 50.

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