Truncated hepatitis b virus (HBV) polymerase polypeptide, fusion protein, vector, host cell, immune composition and kit

Description

Truncated Hepatitis B Virus (HBV) Polymerase Polypeptide, Fusion Protein, Vector, Host Cell, Immunogenic Composition and Kit Separated from BR112022005687-7, filed on 09 / 28 / 2020. CROSS-REFERENCE TO RELATED REQUESTS

[001] This application claims the benefit, under Title 35, § 119(e), of the U.S. Code, of Interim Application No. U.S. 62 / 908,494, filed September 30, 2019, which is incorporated herein by reference in its entirety for all purposes. SEQUENCE LISTING

[002] This request contains a sequence listing that was submitted electronically in ASCII format and is incorporated herein by reference in its entirety. Said ASCII copy, created on September 4, 2020, was named 1324_PF_SL.txt and has a size of 296,675 bytes. BACKGROUND OF THE INVENTION

[003] There have been many attempts to use vaccination to treat patients with chronic hepatitis B virus (HBV) infection to improve HBV surface antigen (sAg) loss rates, the primary marker of functional cure. Such attempts have included vaccination with recombinant proteins (Dikici, et al., J Gastroenterol Hepatol. (2003) 18(2):218-22; Pol, et al., J Hepatol. (2001) 34(6):917-21; Vandepapeliere, et al., Vaccine (2007) 25(51):8585-97; Yalcin, et al. al., J Clin Gastroenterol. (2003) 37(4):330-5; Al-Mahtab, Hepatol Int. (2013) 7(4):981-9; 31(4):221-5), recombinant DNA (Mancini-Bourgine, et al., Hepatology. (2004) 40(4):874-82; Yang, et al., World J Gastroenterol. (2017) 23(2):306-17; Yang, et al., J Viral Hepat. (2012) 19(8):581-93; Yoon, et al., Liver Int. (2015) 35(3):805-15; Cavenaugh, et al., PLoS One. (2011) 6(2):e14626; Petition 870260056387, dated 10 / 06 / 2026, p. 10 / 926 2 / 305 Ther. (2014) 22(3):675-84), dendritic cells (Luo, et al., Vaccine. (2010) 28(13):2497-504; and Wei, et al., Int Immunopharmacol. (2015) 27(2):238-43), a yeast vector (Gane. et al., J Hepatol. (2019) Epub 2019 / 07 / 16. 10.1080 / 21645515.2019.1651141). Despite these many attempts, to date no therapeutic vaccination approach has shown consistent benefit in chronic HBV infection (CHB). Shortcomings in previous vaccine approaches may explain the failures of previous vaccine approaches.

[004] Such deficits include limitations in antigen designs and vaccine technologies used. An optimal antigen will contain highly conserved portions of HBV proteins and exclude poorly conserved regions, since highly conserved regions can induce responses against epitopes that are identical in the vaccine antigen and the virus present in the treated patient, while poorly conserved regions can elicit immunodominant T cell responses against epitopes that are not present in the patient's infecting virus strain (Swadling, et al., Vaccines (Basel). (2016) 4(3). Epub 2016 / 08 / 05. doi: 10.3390 / vaccines4030027. PubMed PMID: 27490575). However, some previous vaccines used antigen designs that do not meet these criteria (Yalcin, et al., J Clin Gastroenterol. (2003) 37(4):330-5; Hoa, et al., above; Yalcin, et al., Infection. (2003) 31(4):221-5; Mancini-Bourgine, et al., above; Yang, et al., J Viral Hepat. (2012) 19(8):581-93; Cavenaugh, et al., above; Godon, et al., above; Gane, et al., above; and Obeng-Adjei, et al., Cancer Gene Ther. (2013) 20(12):652-62). Furthermore, many previous vaccines failed to induce a full combination of CD4+ T cells, virus-specific CD8+ T cells, and antibody responses (Dikici, et al.,. Petition 870260056387, dated 10 / 06 / 2026, page 11 / 926 3 / 305 above; Pol, et al., above; Vandepaperiere, et al., above; Yalcin, et al., J Clin Gastroenterol. (2003) 37(4):330-5; Al-Mahtab, above; Hoa, et al., above; Yalcin, et al., Infection. (2003) 31(4):221-5; Mancini-Bourgine, et al., above; Yang, et al., J Viral Hepat. (2012) 19(8):581-93; Gane. et al., above; and Zoulim, et al., above). These immunological components are particularly important for curing chronic HBV infection, as CD8+ T cells have been shown to be the main effector cells responsible for viral clearance during acute HBV infection in chimpanzees (Thimme, et al., J Virol. (2003) 77(1):68-76). Furthermore, antibodies that bind to the HBV surface antigen (HBsAg) facilitate the elimination of HBsAg and prevent the spread of residual HBV.Furthermore, a high magnitude of immune response is likely required to achieve a therapeutic effect, but many previous CHB vaccines have failed to induce such a robust response (Mancini-Bourgine, et al., above; Yang, et al., J Viral Hepat. (2012) 19(8):581-93; Cavenaugh, et al., above; Gane, et al., above; and Zoulim, et al., above). Finally, some previous CHB vaccine antigens were not sufficiently stable in delivery vectors to allow for commercial-scale vaccine manufacture. SUMMARY OF THE INVENTION

[005] In one aspect, truncated hepatitis B virus (HBV) polymerase polypeptides are provided, for example, capable of inducing or eliciting an immune response in a human after administration. In some embodiments, the truncated HBV polymerase polypeptide comprises an inactivated reverse transcriptase domain and an inactivated RNase H, and does not comprise the entire terminal protein (TP) domain and all or part of the spacer domain. In some embodiments, the polypeptide is no longer than 600 amino acids in length, for example, it is no longer than Petition 870260056387, dated 10 / 06 / 2026, page 12 / 926 4 / 305 which are 595, 590, 585, 580, 575, 570, 565, 560, 555, 550, 545, 540, or 535 amino acids in length. In some embodiments, the reverse transcriptase domain does not comprise a YMDD motif (SEQ ID NO: 97) and the RNase H domain does not comprise an AELL motif (SEQ ID NO: 98). In some embodiments, the YMDD motif (SEQ ID NO: 97) in the reverse transcriptase domain is mutated to YMHD (SEQ ID NO: 99) and the AELL motif (SEQ ID NO: 98) in the RNase H domain is mutated to AHLL (SEQ ID NO: 100). In some embodiments, the polypeptide is of an HBV genotype A, B, C, or D.In some embodiments, (a) the polypeptide is of HBV genotype B and does not comprise a polypeptide sequence (e.g., the sequence is removed or deleted or not included) from SEQ ID NO: 50, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NO: 50; or (b) the polypeptide is of HBV genotype D and does not comprise a polypeptide sequence of SEQ ID NO: 51, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NO: 51. In some embodiments, the truncated HBV polymerase polypeptide comprises or consists of an amino acid sequence of any of the SEQ ID NOs: 13 to 14, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ IDs NOS: 13 to 14.

[006] In another aspect, mutant HBV polymerase deletion polypeptides are provided. In some embodiments, the mutant HBV polymerase deletion polypeptide comprises, in sequential order from the N-terminal to the C-terminal, a terminal protein (TP) domain, an inactivated reverse transcriptase domain, and an inactivated RNase H, wherein the mutant polypeptide does not Petition 870260056387, dated 10 / 06 / 2026, page 13 / 926 5 / 305 comprises all or part of a spacer domain. In some embodiments, the polypeptide is no longer than 800 amino acids in length, for example, it is no longer than 795, 790, 785, 780, 775, 770, 765, 760, 755, 750, 745, 740, 735, 730, 725, 720, 715, 710, or 705 amino acids in length. In some embodiments, the reverse transcriptase domain does not comprise a YMDD motif (SEQ ID NO: 97) and the RNase H domain does not comprise an AELL motif (SEQ ID NO: 98). In some embodiments, the YMDD motif (SEQ ID NO: 97) in the reverse transcriptase domain is mutated to YMHD (SEQ ID NO: 99) and the AELL motif (SEQ ID NO: 98) in the RNase H domain is mutated to AHLL (SEQ ID NO: 100). In some embodiments, the polypeptide is of an HBV genotype A, B, C, or D.In some embodiments, (a) the polypeptide is of HBV genotype A and does not comprise a polypeptide of SEQ ID NO: 42 or 46, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 42 or 46; (b) the polypeptide is of HBV genotype B and does not comprise a polypeptide of SEQ ID NO: 43 or 47, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 43 or 47; (c) the polypeptide is of HBV genotype C and does not comprise a polypeptide of SEQ ID NO: 44 or 48, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 44 or 48; or (d) the polypeptide is of HBV genotype D and does not comprise a polypeptide of SEQ ID NO: 45 or 49, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 45 or 49.In some embodiments, the HBV polymerase deletion mutant polypeptide comprises or consists of an amino acid sequence from any of the SEQ ID NOs: 5 to 12, or a sequence. Petition 870260056387, dated 10 / 06 / 2026, p. 14 / 926 6 / 305 cia that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 5 to 12. In some embodiments, the HBV polymerase deletion mutant polypeptide additionally comprises (e.g., is a fusion protein that includes) an HBV core polypeptide. In some embodiments, the HBV polymerase deletion mutant polypeptide comprises, in sequential order from N-terminal to C-terminal, an HBV core polypeptide and the HBV polymerase deletion mutant polypeptide as described herein. In some embodiments, the HBV polymerase deletion mutant polypeptide comprises or consists of an amino acid sequence from any of the SEQ ID NOs: 19 to 26, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 19 to 26.

[007] In a further aspect, an HBV core-sAg fusion protein is provided. In some embodiments, the core-sAg fusion protein comprises, in sequential order from the N-terminal to the C-terminal, an HBV core polypeptide and an HBV small surface antigen (sAg) polypeptide. In several embodiments, the core polypeptide is of an HBV genotype B or C and the sAg polypeptide is of an HBV genotype C. In some embodiments, the core polypeptide is of an HBV genotype D and the sAg polypeptide is of an HBV genotype D. In some embodiments, the sAg core fusion protein comprises: (a) a core polypeptide comprising or consisting of an amino acid sequence of SEQ ID NO: 65, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to Petition 870260056387, dated 10 / 06 / 2026, p. 15 / 926 7 / 305 SEQ ID NO: 65, and an sAg polypeptide comprising or consisting of an amino acid sequence from SEQ ID NO: 3, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 3; or (b) a core polypeptide comprising or consisting of an amino acid sequence from SEQ ID NO: 66, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 66, and an sAg polypeptide comprising or consisting of an amino acid sequence from SEQ ID NO: 4, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 4.In some embodiments, the core polypeptide comprises a serine (S) residue at the amino acid position corresponding to position 12, and an asparagine (N) residue at the amino acid position corresponding to position 67, wherein the position numbers are reference to SEQ ID NO:65 or SEQ ID NO:66. In some embodiments, the sAg polypeptide comprises an isoleucine (I) residue at the amino acid position corresponding to position 68, and the position numbers are reference to SEQ ID NO:3 or SEQ ID NO:4.In some embodiments, the sAg polypeptide comprises one or more of the following: a serine (S) residue at the amino acid position corresponding to position 53, an isoleucine (I) residue at the amino acid position corresponding to position 68, a threonine (T) residue at the amino acid position corresponding to position 125, a proline (P) residue at the amino acid position corresponding to position 127, a phenylalanine (F) residue at the amino acid position corresponding to position 161, a tyrosine (Y) residue at the amino acid position corresponding to position 200, a serine (S) residue. Petition 870260056387, dated 10 / 06 / 2026, page 16 / 926 8 / 305 at the amino acid position corresponding to position 210, and a leucine (L) residue at the amino acid position corresponding to position 213, wherein the position numbers are reference to SEQ ID NO:3 or SEQ ID NO:4. In several embodiments, the sAg polypeptide does not comprise a pre-S1 polypeptide. In several embodiments, the sAg polypeptide does not comprise a pre-S2 polypeptide. In some embodiments, the sAg polypeptide does not comprise a pre-S2 HBV polypeptide comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 79 to 83, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 79 to 83. In some embodiments, the sAg polypeptide does not comprise both a pre-S1 HBV polypeptide and a pre-S2 HBV polypeptide.In some embodiments, the sAg polypeptide does not comprise a pre-S1-pre-S2 HBV polypeptide comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 84 to 88, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 84 to 88. In several embodiments, the sAg core fusion protein comprises a functionally cleavable linker linked to, and positioned between, the HBV core polypeptide and the HBV sAg polypeptide. In some embodiments, the cleavable linker is a cleavable peptide 2A. In some embodiments, the cleavable linker is a cleavable peptide 2A selected from foot-and-mouth disease virus (F2A), equine rhinitis virus A (E2A), porcine tescovirus-1 (P2A), and Thosea asigna virus (T2A). In some embodiments, the cleavable linker is a porcine tescovirus-1 (P2A) linker.In some embodiments, the cleavable linker comprises or consists of an amino acid sequence of... Petition 870260056387, dated 10 / 06 / 2026, p. 17 / 926 9 / 305 ATNFSLLKQAGDVEENPGP (SEQ ID NO: 56), APVKQTLNFDLLKLAGDVESNPGP (SEQ ID NO: 57), QCTNYALLKLAGDVESNPGP (SEQ ID NO: 58) or EGRGSLLTCGDVEENPGP (SEQ ID NO: 59), or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or at least 99% identical to ATNFSLLKQAGDVEENPGP (SEQ ID NO: 56), APVKQTLNFDLLKLAGDVESNPGP (SEQ ID NO: 57), QCTNYALLKLAGDVESNPGP (SEQ ID NO: 58), or EGRGSLLTCGDVEENPGP (SEQ ID NO: 59). In some embodiments, the cleavable linker comprises or consists of an amino acid sequence of ATNFSLLKQAGDVEENPGP (SEQ ID NO: 56), or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to ATNFSLLKQAGDVEENPGP (SEQ ID NO: 56). In some embodiments, the core-sAg fusion protein comprises a flexible linker and / or a functionally linked furin recognition / cleavage site, positioned at the N-terminus for the cleavable linker and the C-terminus for the HBV core polypeptide.In some embodiments, the furin recognition / cleavage site comprises or consists of an amino acid sequence selected from RAKR (SEQ ID NO: 60), REKR (SEQ ID NO: 61), and RRKR (SEQ ID NO: 62). In some embodiments, the flexible linker comprises a polyglycine or polyalanine sequence. In some embodiments, the flexible linker comprises or consists of a polyglycine or polyalanine sequence selected from AA, AAA, AAY, GG, GGG, GGS, GSG, and GGGS (SEQ ID NO: 63). In some embodiments, the core-sAg fusion protein is no longer than 450 amino acids in length, for example, no longer than 445, 440, 435, 430, 425, 420, 415, or 410 amino acids in length. In some embodiments, the nucleo-sAg fusion protein comprises or consists of an amino acid sequence from any of the SEQ IDs. Petition 870260056387, dated 10 / 06 / 2026, p. 18 / 926 10 / 305 Nos: 38 to 41, for example, SEQ ID NO: 41, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ IDs Nos: 38 to 41, for example, SEQ ID NO: 41. In some embodiments, the fusion polypeptide comprises one or more of the following: a serine (S) residue at the amino acid position corresponding to position 12, an asparagine (N) residue at the amino acid position corresponding to position 67, a valine (V) residue at the amino acid position corresponding to position 74, a phenylalanine (F) residue at the amino acid position corresponding to position 97, a threonine (T) residue at the amino acid position corresponding to position 250, a serine (S) residue at the amino acid position corresponding to position 317, a serine (S) residue at the amino acid position corresponding to position 318, an arginine (R) residue at the amino acid position corresponding to position 326,a tyrosine residue (Y) at the amino acid position corresponding to position 326, a tyrosine residue (Y) at the amino acid position corresponding to position 326, a tyrosine residue (Y) at the amino acid position corresponding to position 338, a glycine residue (G) at the amino acid position corresponding to position 363, and an alanine residue (A) at the amino acid position corresponding to position 372, wherein the position numbers are with reference to SEQ ID NO:41. In several embodiments, the core-sAg fusion polypeptide does not comprise an amino acid sequence or fragment thereof of an HBV protein selected from the group consisting of X, pre-core, pre-S1 and pre-S2.

[008] With respect to HBV immunogenic polypeptides, in some embodiments, the truncated HBV polymerase polypeptide, the mutant HBV polymerase deletion polypeptide, or the nucleolus-sAg fusion protein, as described herein, additionally comprise a signaling peptide or an N initiation sequence. Petition 870260056387, dated 10 / 06 / 2026, page 19 / 926 11 / 305 terminal. In several embodiments, the signaling peptide or initiation sequence is of a protein of origin selected from among a serum protein, a cytokine, a chemokine, a chaperone protein, an invariant protein, and a protein that directs proteins to the lysosomal compartment. In several embodiments, the signaling peptide or initiation sequence is from a protein of selected origin among colony-stimulating factor 2 (CSF2, GM-CSF), tissue-type plasminogen activator (PLAT, t-PA), CC motif chemokine ligand 7 (CCL7, MCP-3), CXC motif chemokine ligand 10 (CXCL10, IP-10), beta-catenin 1 (CTNNB1), CD74 (p33; DHLAG; HLADG; Ia-GAMA, invariant chain), serum albumin (ALB), polyubiquitin B / C (UBB / UBC), calreticulin (CALR), vesicular stomatitis virus protein G (VSV-G), lysosome-associated membrane protein 1 (LAMP-1), and lysosome-associated membrane protein 2 (LAMP-2).In some embodiments, the signaling peptide or initiation sequence is selected from an amino acid sequence of any of the SEQ ID NOs: 67 to 78, or a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 67 to 78. In several embodiments, the truncated HBV polymerase polypeptide, the mutant HBV polymerase deletion polypeptide, and / or the nucleoside-sAg fusion protein, as described herein, may be recombinantly produced or chemically synthesized.In several embodiments, the truncated HBV polymerase polypeptide, the mutant HBV polymerase deletion polypeptide, and / or the nucleus-sAg fusion protein, as described herein, are capable of inducing, promoting, or stimulating an immune response (e.g., expansion and / or activation of CD8+ and / or CD4+ T cells; production of antibodies that bind to and / or neutralize one or more of the HBV polymerase, HBV nucleus, and HBV sAg) in a human. In several embodiments, the truncated HBV polymerase polypeptide, the... Petition 870260056387, dated 10 / 06 / 2026, page 20 / 926 12 / 305 mutant HBV polymerase deletion polypeptide and / or the nucleoside-sAg fusion protein, as described herein, are capable of inducing, promoting, or stimulating an immune response against HBV (e.g., preventing, delaying the progression of, inhibiting, and / or reversing HBV infection) in a human. In various embodiments, the truncated HBV polymerase polypeptide, mutant HBV polymerase deletion polypeptide, and / or the nucleoside-sAg fusion protein, as described herein, are capable of inducing, promoting, or stimulating the proliferation and / or activation of one or more selected cell types from among monocyte-derived dendritic cells (DCs), CD8+ T cells, and CD4+ T cells.

[009] In a further aspect, polynucleotides encoding HBV immunogenic polypeptides are provided, as described herein. For example, polynucleotides encoding one or more of the truncated HBV polymerase polypeptides, the HBV polymerase deletion mutant polypeptide, or the nucleo-sAg fusion protein are provided, as described herein. In some embodiments, the polynucleotide comprises cDNA, mRNA, self-amplifying RNA (SAM), self-replicating RNA, or self-amplifying replicon RNA (RepRNA). In some embodiments, the polynucleotide comprises self-replicating or self-amplifying alphavirus replicons.In some embodiments, the polynucleotide comprises or consists of a nucleic acid sequence of any of the SEQ ID NOs: 27 to 37, for example, SEQ ID NOs: 37 and 89 to 94, for example, SEQ ID NOs: 29, 89, 90 or 92, or which is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 27 to 37, for example, SEQ ID NO: 37 and 89 to 94, for example, SEQ ID NOs: 29, 89, 90 or 92.

[0010] In another aspect, a lipid nanoparticle is provided Petition 870260056387, dated 10 / 06 / 2026, p. 21 / 926 13 / 305 (LNP) comprising one or more of the polynucleotides encoding an immunogenic HBV polypeptide, as described herein.

[0011] In another aspect, expression cassettes are provided comprising one or more of the polynucleotides encoding an immunogenic HBV polypeptide, as described herein, functionally linked to one or more regulatory sequences. In some embodiments, the polynucleotide is functionally linked to, and under the control of, a constitutive promoter. In some embodiments, the promoter is selected from cytomegalovirus (CMV) primary immediate early, chicken beta-actin (CAG) promoter-fused CMV enhancer, human elongation factor 1α (HEF1α), mouse cytomegalovirus (mouse CMV), Chinese hamster elongation factor 1α (CHEF-α), and phosphoglycerate kinase (PGK).

[0012] In another aspect, they are provided comprising one or more of the polynucleotides encoding an immunogenic HBV polypeptide, as described herein, or one or more expression cassettes comprising such polynucleotides. In several embodiments, the vector is a plasmid vector, a bacterial vector, or a viral vector. In some embodiments, the vector is a viral vector. In several embodiments, the viral vector is a DNA virus or an RNA virus. In some embodiments, the viral vector is a virus selected from adenovirus, adeno-associated virus, arenavirus, alphavirus, poxvirus, cytomegalovirus, rhabdovirus, vesicular stomatitis virus, flavivirus, Marabá virus, and vaccinia virus.In some embodiments, the viral vector is a virus from a taxonomic family selected from Adenoviridae, Arenaviridae, Herpesviridae (e.g., cytomegalovirus), Poxviridae (e.g., vaccinia virus, e.g., modified Ankara vaccinia (MVA)), Flaviviridae (e.g., yellow fever virus), Rhabdoviridae (e.g., vesiculovirus, e.g., vesiculovirus). Petition 870260056387, dated 10 / 06 / 2026, page 22 / 926 14 / 305 Marabá), Togaviridae (e.g., alphaviruses). In some embodiments, the viral vector is an arenavirus vector selected from lymphocytic choriomeningitis mamarenavirus (LCMV), Cali mamarenavirus (also called Pichindé mamarenavirus or Pichindé arenavirus (PICV)), Guanarito virus (GTOV), Junín virus (JUNV), Lassa virus (LASV), Lujo virus (LUJV), Machupo virus (MACV), Sabiá virus (SABV), and Whitewater Arroyo virus (WWAV). In some embodiments, the viral vector is an arenavirus vector selected from lymphocytic choriomeningitis mamarenavirus (LCMV) or Cali mamarenavirus (also called Pichindé mamarenavirus or Pichindé arenavirus (PICV)). In some embodiments, the viral vector is a human adenovirus or a simian adenovirus (e.g., a chimpanzee adenovirus, a gorilla adenovirus, or a rhesus adenovirus).In some embodiments, the viral vector is an adenoviral vector selected from adenovirus serotype 5 (Ad5), adenovirus serotype 26 (Ad26), adenovirus serotype 34 (Ad34), adenovirus serotype 35 (Ad35), adenovirus serotype 48 (Ad48), chimpanzee adenovirus (e.g., ChAdOx1, ChAdOx2, ChAd3 (AdC3), ChAd5 (AdC5), ChAd6 (AdC6), ChAd7 (AdC7), ChAd8 (AdC8), ChAd9 (AdC9), ChAd10 (AdC10), ChAd11 (AdC11), ChAd17 (AdC17), ChAd16 (AdC16), ChAd19 (AdC19), ChAd20 (AdC20), ChAd22 (AdC22). ChAd24 (AdC24), ChAdY25, ChAd26 (AdC26), ChAd28 (AdC28), ChAd30 (AdC30), ChAd31 (AdC31), ChAd37 (AdC37), ChAd38 (AdC38), ChAd43 (AdC43), ChAd44 (AdC44), ChAd55 (AdC55), ChAd63 (AdC63), ChAdV63, ChAd68 (AdC68), ChAd73 (AdC73), ChAd82 (AdC82), ChAd83 (AdC83), ChAd143 (AdC143), ChAd144 (AdC144), ChAd145 (AdC145), ChAd147 (AdC147)), gorilla adenovirus (e.g., GC44, GC45, GC46) and rhesus adenovirus (e.g., RhAd51, RhAd52, RhAd53, RhAd54, RhAd55, RhAd56, RhAd57, RhAd58, RhAd59, RhAd60, RhAd61, RhAd62, RhAd63, Petition 870260056387, dated 10 / 06 / 2026, page 23 / 926 15 / 305 RhAd64, RhAd65, RhAd66). In some embodiments, the viral vector is replication-defective, replication-deficient, replication-attenuated, or replication-competent. In some embodiments, the viral vector is a replication-defective arenavirus with a bisegmented genome. In some embodiments, the viral vector is a replication-attenuated arenavirus with a trisegmented genome.

[0013] In an additional aspect, arenaviral vectors are provided. In one embodiment, an arenavirus vector is provided comprising a polynucleotide encoding an HBV nucleoside fusion polypeptide (sAg) comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 38 to 41, for example, SEQ ID NO:41, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 38 to 41, for example, SEQ ID NO:41, and wherein the sAg polypeptide does not comprise an HBV pre-S1 polypeptide and / or an HBV pre-S2 polypeptide. In some embodiments, the core polypeptide comprises a serine (S) residue at the amino acid position corresponding to position 12, and an asparagine (N) residue at the amino acid position corresponding to position 67, wherein the position numbers are reference to SEQ ID NO:65 or SEQ ID NO:66.In some embodiments, the sAg polypeptide comprises an isoleucine (I) residue at the amino acid position corresponding to position 68, and the position numbers are with reference to SEQ ID NO:3 or SEQ ID NO:4. In some embodiments, the sAg polypeptide comprises one or more of a serine (S) residue at the amino acid position corresponding to position 53, an isoleucine (I) residue at the amino acid position corresponding to position 68, a threonine (T) residue at the amino acid position corresponding to position 125, a proline (P) residue at the amino acid position corresponding to position 125, and a proline (P) residue at the amino acid position corresponding to position 125. Petition 870260056387, dated 10 / 06 / 2026, p. 24 / 926 16 / 305 tion 127, a phenylalanine (F) residue at the amino acid position corresponding to position 161, a tyrosine (Y) residue at the amino acid position corresponding to position 200, a serine (S) residue at the amino acid position corresponding to position 210, and a leucine (L) residue at the amino acid position corresponding to position 213, wherein the position numbers are with reference to SEQ ID NO:3 or SEQ ID NO:4. In some embodiments, the sAg core fusion polypeptide comprises one or more of the following: a serine (S) residue at the amino acid position corresponding to position 12, an asparagine (N) residue at the amino acid position corresponding to position 67, a valine (V) residue at the amino acid position corresponding to position 74, a phenylalanine (F) residue at the amino acid position corresponding to position 97, a threonine (T) residue at the amino acid position corresponding to position 249,a threonine (T) residue at the amino acid position corresponding to position 250, a serine (S) residue at the amino acid position corresponding to position 317, a serine (S) residue at the amino acid position corresponding to position 318, an arginine (R) residue at the amino acid position corresponding to position 326, a tyrosine (Y) residue at the amino acid position corresponding to position 338, a glycine (G) residue at the amino acid position corresponding to position 363, and an alanine (A) residue at the amino acid position corresponding to position 372, and the position numbers are with reference to SEQ ID NO:41. In some embodiments, the polynucleotide comprises or consists of a nucleic acid sequence of any of the SEQ ID NOs: 33 to 37, or that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 33 to 37. In some embodiments,The polynucleotide comprises, or consists of, a nucleic acid sequence of SEQ ID NO: 37, or which is at least 80%, 81%, 82%, 83%, Petition 870260056387, dated 10 / 06 / 2026, p. 25 / 926 17 / 305 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 37. In some embodiments, the arenavirus vector has a bisegmented genome and additionally comprises a polynucleotide encoding a truncated HBV polymerase comprising or consisting of an amino acid sequence from any of the SEQ ID NOs: 13 to 14, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 13 to 14, and wherein the truncated HBV polymerase does not comprise the entire HBV terminal protein (TP) domain and does not comprise all or part of an HBV polymerase spacer domain.In some embodiments, the truncated HBV polymerase does not comprise a polypeptide sequence of SEQ ID NO: 50 or SEQ ID NO: 51, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NO: 50 or SEQ ID NO: 51. In some embodiments, the polynucleotide comprises or consists of a nucleic acid sequence of any of the SEQ ID NOs: 29 and 89 to 94, for example, SEQ ID NOs: 29, 89, 90, or 92, or that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 29 and 89 to 94, for example, SEQ ID NOs: 29, 89, 90 or 92.In some embodiments, the arenavirus vector is a lymphocytic choriomeningitis (LCMV) mamarenavirus vector and the polynucleotide comprises or consists of a nucleic acid sequence of SEQ ID NO: 29, or that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NO: 29. In some embodiments, the arenavirus vector is a Cali mamarenavirus vector (also called Pichindé mamarenavirus or Pichindé arenavirus (PICV)) and the polynucleotide. Petition 870260056387, dated 10 / 06 / 2026, p. 26 / 926 18 / 305 tidídeo comprises or consists of a nucleic acid sequence of SEQ ID NO: 90, or is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 90.

[0014] An arenavirus vector is additionally provided comprising a polynucleotide encoding a truncated HBV polymerase comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 13 to 14, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 13 and 14, and wherein the truncated HBV polymerase does not comprise the entire HBV terminal protein (TP) domain and does not comprise all or part of an HBV polymerase spacer domain. In some embodiments, the truncated HBV polymerase does not comprise a polypeptide sequence of SEQ ID NO: 50 or SEQ ID NO: 51, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to either of SEQ ID NO: 50 or SEQ ID NO: 51.In some embodiments, the polynucleotide comprises or consists of a nucleic acid sequence of any of the SEQ ID NOs: 29 and 89 to 94, for example, SEQ ID NOs: 29, 89, 90 or 92, or that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 29 and 89 to 94, for example, SEQ ID NOs: 29, 89, 90 or 92. In some embodiments, the arenavirus vector is a lymphocytic choriomeningitis mamarenavirus vector. (LCMV) and the polynucleotide comprises or consists of a nucleic acid sequence of SEQ ID NO: 29, or that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 29. In some embodiments, the arenavirus vector is... Petition 870260056387, dated 10 / 06 / 2026, p. 27 / 926 19 / 305 a Cali mamarenavirus vector and the polynucleotide comprises or consists of a nucleic acid sequence of SEQ ID NO: 90, or is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 90. In some embodiments, the arenavirus vector is replication-defective, replication-deficient or replication-incompetent.

[0015] In a further aspect, host cells are provided comprising one or more of the polynucleotides encoding an HBV immunogenic polypeptide, as described herein, or one or more vectors comprising such polynucleotides. In some embodiments, the one or more polynucleotides encoding one or more HBV immunogenic polypeptides, as described herein, are not integrated into the host cell genome, for example, they are episomal. In some embodiments, one or more polynucleotides are integrated into the host cell genome. In some embodiments, the host cell is a mammalian cell, for example, a human cell. In several embodiments, the host cell may be in vitro or in vivo.

[0016] In another aspect, immunogenic compositions are provided comprising one or more of the immunogenic HBV polypeptides, as described herein. In some embodiments, the immunogenic composition comprises one or more, for example, two or more of the truncated HBV polymerase polypeptides, one or more, for example, two or more of the mutant HBV polymerase polypeptides, and / or one or more, for example, two or more of the nucleoside-sAg fusion proteins, as described herein. In some embodiments, the immunogenic composition comprises one or more, for example, two or more polynucleotides encoding one or more, for example, two or more of the truncated polypeptides. Petition 870260056387, dated 10 / 06 / 2026, page 28 / 926 20 / 305 HBV merase, one or more, for example, two or more of the mutant HBV polymerase deletion polypeptides and / or one or more, for example, two or more of the nucleo-sAg fusion proteins, as described herein. In some embodiments, the immunogenic composition comprises one or more, for example, two or more, vectors comprising one or more, for example, two or more, polynucleotides encoding one or more, for example, two or more, of the truncated HBV polymerase polypeptides, one or more, for example, two or more, of the mutant HBV polymerase deletion polypeptides and / or one or more, for example, two or more of the nucleo-sAg fusion proteins, as described herein. The immunogenic compositions further comprise a pharmaceutically acceptable carrier. In some forms, the immunogenic composition comprises one or more polynucleotides in the form of self-replicating DNA, cDNA, mRNA, or RNA.In several embodiments, the immunogenic composition comprises a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide encoding a truncated HBV polymerase polypeptide or a mutant HBV polymerase deletion polypeptide, as described herein; and (b) the second viral expression vector comprises a polynucleotide encoding the nucleoside-sAg fusion protein, as described. In some embodiments, the immunogenic composition comprises a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide encoding a mutant HBV polymerase polypeptide comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 5 to 14, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%,. Petition 870260056387, dated 10 / 06 / 2026, p. 29 / 926 21 / 305 (a) the first viral expression vector comprises a polynucleotide encoding the nucleo-sAg fusion protein comprising or consisting of an amino acid sequence from any of the SEQ ID NOs: 38 to 41, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 38 to 41.In some embodiments, the immunogenic composition comprises a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide encoding a mutant HBV polymerase polypeptide comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 13 to 14, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 13 to 14; and (b) the second viral expression vector comprises a polynucleotide encoding the nucleo-sAg fusion protein comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 38 to 41, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 38 to 41.In some embodiments, the immunogenic compositions comprise a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide encoding a mutant HBV polymerase polypeptide comprising or consisting of an amino acid sequence of SEQ ID NO: 13, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,. Petition 870260056387, dated 10 / 06 / 2026, page 30 / 926 22 / 305 96%, 97%, 98% or 99% identical to SEQ ID NO: 13; (b) the second viral expression vector comprises a polynucleotide encoding the core-sAg fusion protein comprising or consisting of an amino acid sequence from SEQ ID NO: 41, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 41. In some embodiments, the core polypeptide comprises a serine (S) residue at the amino acid position corresponding to position 12, and an asparagine (N) residue at the amino acid position corresponding to position 67, wherein the position numbers are with reference to SEQ ID NO: 65 or SEQ ID NO: 66. In some embodiments, the sAg polypeptide comprises an isoleucine (I) residue at the amino acid position corresponding to position 68, and the position numbers are with reference to SEQ ID NO:3 or SEQ ID NO:4.In some embodiments, the sAg polypeptide comprises one or more of the following: a serine (S) residue at the amino acid position corresponding to position 53, an isoleucine (I) residue at the amino acid position corresponding to position 68, a threonine (T) residue at the amino acid position corresponding to position 125, a proline (P) residue at the amino acid position corresponding to position 127, a phenylalanine (F) residue at the amino acid position corresponding to position 161, a tyrosine (Y) residue at the amino acid position corresponding to position 200, a serine (S) residue at the amino acid position corresponding to position 210, and a leucine (L) residue at the amino acid position corresponding to position 213, wherein the position numbers are with reference to SEQ ID NO:3 or SEQ ID NO:4.In some embodiments, the sAg core fusion polypeptide comprises one or more of a serine (S) residue at the amino acid position corresponding to position 12, an asparagine (N) residue at the position. Petition 870260056387, dated 10 / 06 / 2026, page 31 / 926 23 / 305 of an amino acid corresponding to position 67, a valine (V) residue at the amino acid position corresponding to position 74, a phenylalanine (F) residue at the amino acid position corresponding to position 97, a threonine (T) residue at the amino acid position corresponding to position 249, a threonine (T) residue at the amino acid position corresponding to position 250, a serine (S) residue at the amino acid position corresponding to position 317, a serine (S) residue at the amino acid position corresponding to position 318, an arginine (R) residue at the amino acid position corresponding to position 326, a tyrosine (Y) residue at the amino acid position corresponding to position 338, a glycine (G) residue at the amino acid position corresponding to position 363, and an alanine (A) residue at the amino acid position corresponding to position 372, where the position numbers are with reference to SEQ ID NO:41.In some embodiments, the immunogenic compositions comprise a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of any of the SEQ ID NOs: 27 to 32 and 89 to 94, for example, SEQ ID NOs: 29, 89, 90 or 92, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 27 to 32 and 89 to 94, for example, SEQ ID (a) the second viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of any of the SEQ IDs 33 to 37 or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ IDs 33 to 37.In some modalities, the composition is immunological. Petition 870260056387, dated 10 / 06 / 2026, p. 32 / 926 24 / 305 nogenic comprises a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of SEQ ID NO: 29 or 90, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 29 or 90; and (b) the second viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 37 or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 37.In several embodiments, the first viral expression vector and the second viral expression vector are independently selected from a taxonomic family among Adenoviridae, Arenaviridae, Herpesviridae (e.g., cytomegalovirus), Poxviridae (e.g., vaccinia virus, e.g., modified Ankara vaccinia (MVA)), Flaviviridae (e.g., yellow fever virus), Rhabdoviridae (e.g., vesiculovirus, e.g., Marabá vesiculovirus), Togaviridae (e.g., alphavirus). In several embodiments, the first viral expression vector and the second viral expression vector in the immunogenic composition may be from the same taxonomic family or from different taxonomic families. In some embodiments, the first viral expression vector and the second viral expression vector in the immunogenic composition are from Arenaviridae.In some embodiments, the first viral expression vector and the second viral expression vector in the immunogenic composition are independently selected from an arenavirus vector among lymphocytic choriomeningitis mamarenavirus (LCMV), Cali mamarenavirus (also called Pichindé mamarenavirus or Pichindé arenavirus (PICV)), Guanarito virus (GTOV). Petition 870260056387, dated 10 / 06 / 2026, page 33 / 926 25 / 305 Junín virus (JUNV), Lassa virus (LASV), Lujo virus (LUJV), Machupo virus (MACV), Sabiá virus (SABV), and Whitewater Arroyo virus (WWAV). In some embodiments, the first viral expression vector and the second viral expression vector are independently selected from an arenavirus vector among lymphocytic choriomeningitis mamarenavirus (LCMV) or Cali mamarenavirus (also called Pichindé mamarenavirus or Pichindé arenavirus (PICV)). In some embodiments, the first viral expression vector and the second viral expression vector are replication-defective or replication-deficient. In some embodiments, the first viral expression vector and the second viral expression vector are attenuated for replication.In some embodiments, the immunogenic composition comprises a first LCMV arenavirus expression vector and a second LCMV arenavirus expression vector, wherein: (a) the first LCMV arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 29, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 29; and (b) the second LCMV arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 37 or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 37.In some embodiments, the immunogenic composition comprises a first Pichindé arenavirus expression vector and a second Pichindé arenavirus expression vector, wherein: (a) the first Pichindé arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of SEQ ID NO: 90, or a. Petition 870260056387, dated 10 / 06 / 2026, page 34 / 926 26 / 305 sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 90; (b) the second Pichindé arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 37 or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 37. In various embodiments, the first viral expression vector and the second viral expression vector are provided in the immunogenic composition in a ratio in the range of 1:10 to 10:1, for example, 1:9 to 9:1, 1:8 to 8:1, 1:7 to 7:1, 1:6 to 6:1, 1:5 to 5:1, 1:4 to 4:1, 1:3 to 3:1, 1:2 to 2:1 or 1:1.In some embodiments, the immunogenic composition comprises in the range of about 10³ to about 10¹² focus-forming units (FFUs) or plaque-forming units (PFUs) or viral infectious units (IUs) or viral particles (vp) per milliliter, for example, from about 10⁴ to about 10⁷ FFUs or PFUs or viral IUs or vp per milliliter, for example, from about 10³ to about 10⁴, 10⁵, 10⁶, 10⁷, 10⁸, 10⁹, 10¹⁰, 10¹¹ or 10¹² FFUs or PFUs or viral IUs or vp per milliliter, of each of the first viral expression vector and the second viral expression vector. In some embodiments, the immunogenic composition further comprises one or more of an adjuvant, a detergent, a micelle-forming agent, and an oil. In various forms, the immunogenic composition is formulated for administration via a selected route from intravenous, intramuscular, intradermal, subcutaneous, and mucosal (e.g., buccal, intranasal, intrarectal, intravaginal).In some embodiments, the immunogenic composition is an aqueous solution or suspension; for example, it is formulated as a liquid. In some embodiments, the immunogenic composition is lyophilized. Petition 870260056387, dated 10 / 06 / 2026, page 35 / 926 27 / 305

[0017] In another aspect, kits are provided. In various embodiments, the kit comprises one or more, for example, two or more unit doses of one or more, for example, two or more, of a truncated HBV polymerase polypeptide, one or more, for example, two or more, of an HBV polymerase deletion mutant polypeptide and / or one or more, for example, two or more, of a nucleo-sAg fusion protein, as described herein. In some embodiments, the kit comprises one or more, for example, two or more, unit doses of one or more, for example, two or more, polynucleotides encoding one or more, for example, two or more, of a truncated HBV polymerase polypeptide, one or more, for example, two or more, of an HBV polymerase deletion mutant polypeptide and / or one or more, for example, two or more, of a nucleo-sAg fusion protein, as described herein.In some embodiments, the kit comprises one or more, for example, two or more, unit doses of one or more, for example, two or more, vectors comprising one or more, for example, two or more, polynucleotides encoding one or more, for example, two or more, of a truncated HBV polymerase polypeptide, one or more, for example, two or more, of a mutant HBV polymerase deletion polypeptide, and / or one or more, for example, two or more, of a nucleo-sAg fusion protein, as described herein. In several embodiments, the kit comprises one or more, for example, two or more unit doses of one or more, for example, two or more immunogenic compositions, as described herein. In some embodiments, the one or more unit doses in the kit are in a single container. In some embodiments, the one or more unit doses in the kit are in two or more separate containers.In some embodiments, the kit comprises one or more containers selected from among vials, ampoules, and pre-filled syringes. In some embodiments, the kit comprises one or more containers that comprise... Petition 870260056387, dated 10 / 06 / 2026, page 36 / 926 28 / 305 dem one or more polypeptides, one or more polynucleotides, one or more vectors or one or more immunogenic compositions in an aqueous solution or suspension or as a lyophilized preparation. In various embodiments, the one or more unit doses may be the same or different. In some embodiments, the kit comprises one or more unit doses of one or more viral vectors, as described herein, wherein the unit doses are in the range of approximately 10³ to approximately 10¹² focus-forming units (FFU) or plaque-forming units (PFU) or viral infectious units (UI) or viral particles (vp), for example, from approximately 10⁴ to approximately 10⁷ FFU or PFU or viral UI or vp, for example, from approximately 10³ to approximately 10⁴, 10⁵, 10⁶, 10⁷, 10⁸, 10⁹, 10¹⁰, 10¹¹ or 10¹² FFU or PFU or viral UI or vp.In some embodiments, the kit comprises one or more coding polynucleotides, or one or more expressing vectors, or an immunogenic composition comprising at least two immunogenic polypeptides, wherein the immunogenic polypeptides comprise: (a) a mutant HBV polymerase polypeptide comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 5 to 14, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 5 to 14; and (b) an HBV-sAg core fusion protein comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 38 to 41, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 38 to 41.In some embodiments, the kit comprises one or more coding polynucleotides, or one or more expressing vectors, or an immunogenic composition comprising at least two immunogenic polypeptides, wherein the immunogenic polypeptides comprise: (a) a polypeptide. Petition 870260056387, dated 10 / 06 / 2026, page 37 / 926 29 / 305 mutant HBV polymerase dinucleotide comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 13 to 14, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 13 to 14; and (b) an HBV-sAg core fusion protein comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 38 to 41, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 38 to 41.In some embodiments, the kit comprises one or more coding polynucleotides, or one or more expressing vectors, or an immunogenic composition comprising at least two immunogenic polypeptides, wherein the immunogenic polypeptides comprise: (a) a mutant HBV polymerase polypeptide comprising or consisting of an amino acid sequence of SEQ ID NO: 13, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 13; and (b) an HBV core-sAg fusion protein comprises or consists of an amino acid sequence from SEQ ID NO: 41, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 41.In some embodiments, the core polypeptide comprises a serine (S) residue at the amino acid position corresponding to position 12, and an asparagine (N) residue at the amino acid position corresponding to position 67, wherein the position numbers are referenced to SEQ ID NO:65 or SEQ ID NO:66. In some embodiments, the sAg polypeptide comprises an isoleucine (I) residue at the amino acid position corresponding to position 68, and the position numbers are referenced to SEQ ID NO:65. Petition 870260056387, dated 10 / 06 / 2026, p. 38 / 926 30 / 305 positions are with reference to SEQ ID NO:3 or SEQ ID NO:4. In some embodiments, the sAg polypeptide comprises one or more of the following: a serine (S) residue at the amino acid position corresponding to position 53, an isoleucine (I) residue at the amino acid position corresponding to position 68, a threonine (T) residue at the amino acid position corresponding to position 125, a proline (P) residue at the amino acid position corresponding to position 127, a phenylalanine (F) residue at the amino acid position corresponding to position 161, a tyrosine (Y) residue at the amino acid position corresponding to position 200, a serine (S) residue at the amino acid position corresponding to position 210, and a leucine (L) residue at the amino acid position corresponding to position 213, wherein the position numbers are with reference to SEQ ID NO:3 or SEQ ID NO:4. In some sports,The sAg core fusion polypeptide comprises one or more of the following: a serine residue (S) at the amino acid position corresponding to position 12, an asparagine residue (N) at the amino acid position corresponding to position 67, a valine residue (V) at the amino acid position corresponding to position 74, a phenylalanine residue (F) at the amino acid position corresponding to position 97, a threonine residue (T) at the amino acid position corresponding to position 249, a threonine residue (T) at the amino acid position corresponding to position 250, a serine residue (S) at the amino acid position corresponding to position 317, a serine residue (S) at the amino acid position corresponding to position 318, an arginine residue (R) at the amino acid position corresponding to position 326, a tyrosine residue (Y) at the amino acid position corresponding to position 338, a glycine residue (G) at the amino acid position corresponding to position 339, and a glycine residue (G) at the amino acid position corresponding to position 339. to position 363,and an alanine (A) residue at the amino acid position corresponding to position 372, and the position numbers are with reference to SEQ ID NO:41. In some embodiments, the kit with, Petition 870260056387, dated 10 / 06 / 2026, p. 39 / 926 31 / 305 comprises first and second vectors encoding first and second immunogenic polypeptides, respectively, wherein the first and second immunogenic polypeptides comprise, respectively: (a) a mutant HBV polymerase polypeptide comprising or consisting of an amino acid sequence from SEQ ID NO: 13, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 13; and (b) an HBV-sAg core fusion protein comprises or consists of an amino acid sequence from SEQ ID NO: 41, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 41.In some embodiments, the kit comprises a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of any of the SEQ ID NOs: 27 to 32 and 89 to 94, for example, SEQ ID NOs: 29, 89, 90 or 92, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 27 to 32 and 89 to 94, for example, SEQ ID NOs: (a) the second viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of any of the SEQ ID NOs: 33 to 37, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 33 to 37.In some embodiments, the kit comprises a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence. Petition 870260056387, dated 10 / 06 / 2026, page 40 / 926 32 / 305 of SEQ ID NO: 29 or 90, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 29 or 90; (b) the second viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 37, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37. In some embodiments, the kit comprises one or more unit doses of an immunogenic composition comprising first and second viral expression vectors, as described herein, wherein the first and second viral expression vectors comprise a replication-deficient or replication-defective Cali mamarenavirus (also called Pichindé mamarenavirus or Pichindé arenavirus (PICV)).In some embodiments, the kit comprises one or more unit doses of an immunogenic composition comprising first and second viral expression vectors, as described herein, wherein the first and second viral expression vectors comprise a replication-deficient or replication-defective lymphocytic choriomeningitis mamarenavirus (LCMV). In some embodiments, the kit comprises (a) one or more unit doses of an immunogenic composition, as described herein, wherein the first and second viral expression vectors are Adenoviridae; and (b) one or more unit doses of an immunogenic composition, as described herein, wherein the first and second viral expression vectors are Poxviridae (e.g., vaccinia virus, e.g., modified Ankara vaccinia (MVA)).In some embodiments, the kit comprises (a) one or more unit doses of an immunogenic composition, as described herein, wherein the first and second viral expression vectors are Adenoviridae; and (b) one or more unit doses of a compound. Petition 870260056387, dated 10 / 06 / 2026, page 41 / 926 33 / 305 immunogenic position, as described herein, wherein the first and second viral expression vectors are Adenoviridae. In some embodiments, the kit comprises a first LCMV arenavirus expression vector and a second LCMV arenavirus expression vector, wherein: (a) the first LCMV arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 29, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 29; and (b) the second LCMV arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 37, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 37.In some embodiments, the kit comprises a first Pichindé arenavirus expression vector and a second Pichindé arenavirus expression vector, wherein: (a) the first Pichindé arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 90, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 90; (b) the second Pichindé arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of SEQ ID NO: 37, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 37. In several embodiments, the kit further comprises one or more unit doses of one or more additional therapeutic agents.In some forms, the kit additionally includes one or more agonists or activators of one or more receptors. Petition 870260056387, dated 10 / 06 / 2026, p. 42 / 926 34 / 305 Toll-like receptors (TLRs). In some embodiments, the kit additionally comprises one or more TLR agonists or activators selected from a TLR2 agonist, a TLR3 agonist, a TLR4 agonist, a TLR5 agonist, a TLR7 agonist, a TLR8 agonist, and a TLR9 agonist. In some embodiments, the kit additionally comprises a TLR7 agonist selected from GS 9620 (vesatolimod), R848 (resiquimod), DS-0509, LHC-165, and TMX-101 (imiquimod). In some embodiments, the kit additionally comprises a TLR8 agonist selected from GS-9688, R848 (resiquimod), and NKTR-262 (dual TLR7 / TLR8 agonist). In some embodiments, the kit additionally comprises one or more interleukin receptor agonists selected from IL-2, IL-7, IL-12, and IL-15. In some embodiments, the kit additionally comprises one or more cytokines selected from IL-2, IL-7, IL-12, IL-15, and variants thereof.In some embodiments, the kit additionally comprises one or more innate immune activators. In some embodiments, the kit comprises one or more innate immune activators comprising an agonist of a receptor selected from fms-related tyrosine kinase 3 (FLT3), receptor stimulator of interferon genes (STING), DExD / H-box helicase 58 (DDX58; also called RIG-I), nucleotide-binding oligomerization domain-containing protein 2 (NOD2). In some embodiments, the kit additionally comprises one or more unit doses of GS-3583 and / or GS-9992. In some embodiments, the kit additionally comprises one or more inhibitors or antagonists of an immune checkpoint receptor or protein and / or one or more activators or agonists of an immune checkpoint receptor or protein.In some embodiments, the kit additionally comprises one or more immune checkpoint receptors or proteins selected from CD27, CD70; CD40, CD40LG;. Petition 870260056387, dated 10 / 06 / 2026, page 43 / 926 35 / 305 CD47, CD48 (SLAMF2), transmembrane domain-containing immunoglobulin protein 2 (TMIGD2, CD28H), CD84 (LY9B, SLAMF5), CD96, CD160, MS4A1 (CD20), CD244 (SLAMF4); CD276 (B7H3); Vset domain-containing T-cell activation inhibitor 1 (VTCN1, B7H4); V-set domain-containing immunoregulatory receptor (VSIR, B7H5, VISTA); immunoglobulin superfamily member 11 (IGSF11, VSIG3); natural killer cell cytotoxicity receptor ligand 3 (NCR3LG1, B7H6); HERV-H LTR-associated protein 2 (HHLA2, B7H7); T-cell inducible co-stimulatory molecule (ICOS, CD278); T-cell inducible co-stimulatory ligand (ICOSLG, B7H2); TNF receptor superfamily member 4 (TNFRSF4, OX40); TNF superfamily member 4 (TNFRSF4, OX40L); TNFRSF8 (CD30), TNFSF8 (CD30L); TNFRSF10A (CD261, DR4, TRAILR1), TNFRSF9 (CD137), TNFSF9 (CD137L); TNFRSF10B (CD262, DR5, TRAILR2), TNFRSF10 (TRAIL); TNFRSF14 (HVEM, CD270), TNFSF14 (HVEML); CD272 (associated with B and T lymphocytes (BTLA));TNFRSF17 (BCMA, CD269), TNFSF13B (BAFF); TNFRSF18 (GITR), TNFSF18 (GITRL); MHC class I polypeptide-related sequence A (MICA); MHC class I polypeptide-related sequence B (MICB); CD274 (CD274, PDL1, PD-L1); programmed cell death 1 (PDCD1, PD1, PD-1); T-cell-associated cytotoxic protein 4 (CTLA4, CD152); CD80 (B7-1), CD28; nectin cell adhesion molecule 2 (NECTIN2, CD112); CD226 (DNAM-1); poliovirus receptor (PVR) cell adhesion molecule (PVR, CD155); PVR-related immunoglobulin domain-containing (PVRIG, CD112R); T-cell immunoreceptor with Ig and ITIM domains (TIGIT); protein 4 containing mucin domain and T cell immunoglobulin (TIMD4; TIM4); hepatitis A virus cell receptor 2 (HAVCR2, TIMD3, TIM3); galectin 9 (LGALS9); lymphocyte activation 3 (LAG3, CD223); lymphocyte activation molecule signaling family member 1 (SLAMF1, SLAM, CD150); lymphocyte antigen 9 (LY9, CD229, SLAMF3);Member 6 of the SLAM family; Petition 870260056387, dated 10 / 06 / 2026, p. 44 / 926 36 / 305 (SLAMF6, CD352); SLAM family member 7 (SLAMF7, CD319); UL16-binding protein 1 (ULBP1); UL16-binding protein 2 (ULBP2); UL16-binding protein 3 (ULBP3); early transcription of retinoic acid 1E (RAET1E; ULBP4); early transcription of retinoic acid 1G (RAET1G; ULBP5); early transcription of retinoic acid 1L (RAET1L; ULBP6); lymphocyte activator gene 3 (CD223); killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR, CD158E1); killer cell lectin-like receptor C1 (KLRC1, NKG2A, CD159A); Killer cell lectin-like K1 receptor (KLRK1, NKG2D, CD314); Killer cell lectin-like C2 receptor (KLRC2, CD159c, NKG2C); Killer cell lectin-like C3 receptor (KLRC3, NKG2E); Killer cell lectin-like C4 receptor (KLRC4, NKG2F);Killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 1 (KIR2DL1); Killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 2 (KIR2DL2); Killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 3 (KIR2DL3); Killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR3DL1); Killer cell lectin-like receptor D1 (KLRD1); SLAM family member 7 (SLAMF7). In some embodiments, the kit comprises one or more blockers or inhibitors of one or more T-cell inhibitory immune checkpoint receptors or proteins. In some embodiments, the kit further comprises one or more T-cell inhibitory immune checkpoint receptors or proteins selected from CD274 (CD274, PDL1, PD-L1);programmed cell death ligand 1 (PDCD1LG2, PD-L2, CD273); programmed cell death 1 (PDCD1, PD1, PD-1); T-cell associated cytotoxic protein 4 (CTLA4); Petition 870260056387, dated 10 / 06 / 2026, page 45 / 926 37 / 305 CD152); CD276 (B7H3); V-set domain containing T-cell activation inhibitor 1 (VTCN1, B7H4); immunoregulatory receptor with VSet domain (VSIR, B7H5, VISTA); immunoglobulin superfamily member 11 (IGSF11, VSIG3); TNFRSF14 (HVEM, CD270), TNFSF14 (HVEML); CD272 (associated with B and T lymphocytes (BTLA)); containing PVR-related immunoglobulin domain (PVRIG, CD112R); T-cell immunoreceptor with Ig and ITIM domains (TIGIT); lymphocyte activation 3 (LAG3, CD223); hepatitis A virus cell receptor 2 (HAVCR2, TIMD3, TIM3); galectin 9 (LGALS9); Killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR, CD158E1); Killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 1 (KIR2DL1); Killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 2 (KIR2DL2);Killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 3 (KIR2DL3); and killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR3DL1). In some embodiments, the kit additionally comprises one or more agonists or activators of one or more T cell-stimulating immune checkpoint receptors or proteins. In some embodiments, the kit additionally comprises one or more T cell-stimulating immune checkpoint receptors or proteins selected from CD27, CD70, CD40, CD40LG; inducible T-cell co-stimulator (ICOS, CD278); inducible T-cell co-stimulator ligand (ICOSLG, B7H2); TNF receptor superfamily member 4 (TNFRSF4, OX40); TNF superfamily member 4 (TNFSF4, OX40L); TNFRSF9 (CD137), TNFSF9 (CD137L); TNFRSF18 (GITR), TNFSF18 (GITRL); CD80 (B7-1), CD28; nectin cell adhesion molecule 2 (NECTIN2, CD112); CD226 (DNAM-1); poliovirus receptor (PVR) cell adhesion molecule (PVR, CD155). Petition 870260056387, dated 10 / 06 / 2026, page 46 / 926 38 / 305 In some embodiments, the kit additionally comprises one or more unit doses of AGEN-2373 and / or AGEN-1223. In some embodiments, the kit additionally comprises one or more blockers or inhibitors of one or more immune checkpoint receptors or proteins that inhibit NK cells.In some embodiments, the kit additionally comprises one or more immune checkpoint receptors or NK cell inhibitors selected from killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR, CD158E1); killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 1 (KIR2DL1); killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 2 (KIR2DL2); killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 3 (KIR2DL3); killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR3DL1); killer cell lectin-like C1 receptor (KLRC1, NKG2A, CD159A); and killer cell lectin-like D1 receptor (KLRD1, CD94).In some embodiments, the kit additionally comprises one or more agonists or activators of one or more NK cell-stimulating immune checkpoint receptors or proteins. In some embodiments, the kit additionally comprises one or more NK cell-stimulating immune checkpoint receptors or proteins selected from CD16, CD226 (DNAM-1); killer cell lectin-like K1 receptor (KLRK1, NKG2D, CD314); SLAM family member 7 (SLAMF7). In some embodiments, the kit additionally comprises one or more PD-L1 (CD274), PD-1 (PDCD1) and / or CTLA4 proteinaceous inhibitors. In some embodiments, the kit additionally comprises one or more CTLA4 proteinaceous inhibitors selected from ipilimumab, Petition 870260056387, dated 10 / 06 / 2026, page 47 / 926. 39 / 305 melimumabe, BMS-986218, AGEN1181, AGEN1884, BMS-986249, MK1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN-2041, JHL-1155, KN-044, CG-0161, ATOR1144, PBI-5D3H5, FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4) e AK-104 (CTLA4 / PD-1). Em algumas modalidades, o kit compreende adicionalmente um ou mais inibidores proteináceos de PD-L1 (CD274) ou PD-1 (PDCD1) selecionados dentre zimberelimabe (AB122), pembrolizumabe, nivolumabe, cemiplimabe, pidilizumabe, AMP-224, MEDI0680 (AMP-514), spartalizumabe, atezolizumabe, avelumabe, ASC22, durvalumabe, BMS-936559, CK-301, PF-06801591, BGB-A317 (tislelizumabe), GLS-010 (WBP-3055), AK-103 (HX-008), AK-105, CS-1003, HLX-10, MGA-012, BI-754091, AGEN2034, JS-001 (toripalimabe), JNJ-63723283, genolimzumabe (CBT-501), LZM-009, BCD-100, LY-3300054, SHR-1201, SHR-1210 (camrelizumabe), Sym-021, ABBV-181, PD1-PIK,BAT-1306, (MSB0010718C), CX072, CBT-502, TSR-042 (dostarlimab), MSB-2311, JTX-4014, BGBA333, SHR-1316, CS-1001 (WBP-3155, KN-035, IBI-308 (sintilimab), HLX-20, KL-A167, STI-A1014, STI-A1015 (IMC-001), BCD-135, FAZ053, TQB-2450, MDX1105-01, FPT-155 (CTLA4 / PD-L1 / CD28), PF06936308 (PD-1 / CTLA4), MGD-013 (PD-1 / LAG-3), FS-118 (LAG-3 / PDL1) MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), RO-7121661 (PD-1 / TIM-3), XmAb-20717 (PD-1 / CTLA4), AK-104 (CTLA4 / PD-1), M7824 (domain EC of PD-L1 / TGFe), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM3 / PDL1) and, INBRX-105 (4-1BB / PDL1). In some embodiments, the kit additionally comprises one or more small molecule inhibitors of CD274 (PDL1, PD-L1), programmed cell death 1 (PDCD1, PD1, PD-1) and / or CTLA4. In some embodiments, the kit additionally comprises one or more small molecule inhibitors of CD274 or PDCD1 selected Petition 870260056387, dated 10 / 06 / 2026, page 48 / 926 40 / 305 born from GS-4224, GS-4416, INCB086550 and MAX10181. In some embodiments, the kit additionally comprises the CTLA4 small molecule inhibitor, BPI-002. In some embodiments, the kit additionally comprises one or more antiviral agents. In some embodiments, the kit additionally comprises one or more antiviral agents selected from lamivudine (LAM), adefovir dipivoxil (ADV), entecavir (ETV), telbivudine (LdT), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF or VEMLIDY®) and ledipasvir + sofosbuvir (HARVONI®).In some embodiments, the kit additionally comprises one or more therapeutic agents selected from among HBV antigen inhibitors (e.g., HBV core antigen inhibitors (HBcAg), HBV surface antigen inhibitors (HBsAg), HBx inhibitors, HBV E antigen inhibitors), HBV anti-antigen antibodies, HBV-targeted inhibitory nucleic acids (e.g., antisense oligonucleotide, short interfering RNA (siRNA), DNA-targeted interfering RNA (ddRNAi)), HBV-targeted gene editors (e.g., CRISPR-Cas (e.g., Cas9, Cas12, Cascade, Cas13), zinc finger nucleases, guided endonucleases, guided meganucleases (e.g., ARCUS), synthetic nucleases, TALENs), covalently closed circular DNA (cccDNA) inhibitors, and HBsAg secretion or assembly inhibitors and entry inhibitors. HBV viral infection.

[0018] In a further aspect, methods are provided for eliciting an immune response to the human hepatitis B virus (HBV) in an individual who needs them. Methods for treating or preventing the human hepatitis B virus (HBV) are also provided in an individual who needs them. In some embodiments, the methods comprise administering to the individual a therapeutically effective amount of one or more immunogenic compositions, as described herein. In some embodiments, the Petition 870260056387, dated 10 / 06 / 2026, p. 49 / 926 41 / 305 methods involve administering one or more immunogenic compositions comprising a mixture comprising a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide encoding a truncated HBV polymerase polypeptide or a mutant HBV polymerase deletion polypeptide, as described herein;and (b) the second viral expression vector comprises a polynucleotide encoding the Ag nucleofusion protein, as described herein. In some embodiments, the methods involve administering to the individual a therapeutically effective amount of one or more immunogenic compositions comprising a mixture comprising a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide encoding a mutant HBV polymerase polypeptide comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 5 to 14, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 5 to 14;and (b) the second viral expression vector comprises a polynucleotide encoding the nucleoside-sAg fusion protein comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 38 to 41, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 38 to 41. In some embodiments, the methods involve administering to the individual a therapeutically effective amount of one or more immunogenic compositions comprising a mixture comprising a first viral expression vector and a second viral expression vector, wherein: (a) the pri; Petition 870260056387, dated 10 / 06 / 2026, p. 50 / 926 42 / 305 first viral expression vector comprises a polynucleotide encoding a mutant HBV polymerase polypeptide comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 13 to 14, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 13 to 14; and (b) the second viral expression vector comprises a polynucleotide encoding the nucleo-sAg fusion protein comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 38 to 41, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 38 to 41.In some embodiments, the methods involve administering to the individual a therapeutically effective amount of one or more immunogenic compositions comprising a mixture comprising a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide encoding a mutant HBV polymerase polypeptide comprising or consisting of an amino acid sequence of SEQ ID NO: 13, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 13; and (b) the second viral expression vector comprises a polynucleotide encoding the nucleo-sAg fusion protein comprising or consisting of an amino acid sequence from SEQ ID NO: 41, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 41.In some embodiments, the core polypeptide comprises a serine (S) residue at the core amino acid position. Petition 870260056387, dated 10 / 06 / 2026, page 51 / 926 43 / 305 corresponding to position 12, and an asparagine residue (N) at the amino acid position corresponding to position 67, with the position numbers referring to SEQ ID NO:65 or SEQ ID NO:66. In some embodiments, the sAg polypeptide comprises an isoleucine residue (I) at the amino acid position corresponding to position 68, and the position numbers refer to SEQ ID NO:3 or SEQ ID NO:4.In some embodiments, the sAg polypeptide comprises one or more of the following: a serine (S) residue at the amino acid position corresponding to position 53, an isoleucine (I) residue at the amino acid position corresponding to position 68, a threonine (T) residue at the amino acid position corresponding to position 125, a proline (P) residue at the amino acid position corresponding to position 127, a phenylalanine (F) residue at the amino acid position corresponding to position 161, a tyrosine (Y) residue at the amino acid position corresponding to position 200, a serine (S) residue at the amino acid position corresponding to position 210, and a leucine (L) residue at the amino acid position corresponding to position 213, wherein the position numbers are with reference to SEQ ID NO:3 or SEQ ID NO:4.In some embodiments, the sAg core fusion polypeptide comprises one or more of the following: a serine (S) residue at the amino acid position corresponding to position 12, an asparagine (N) residue at the amino acid position corresponding to position 67, a valine (V) residue at the amino acid position corresponding to position 74, a phenylalanine (F) residue at the amino acid position corresponding to position 97, a threonine (T) residue at the amino acid position corresponding to position 249, a threonine (T) residue at the amino acid position corresponding to position 250, a serine (S) residue at the amino acid position corresponding to position 317, a serine (S) residue at the amino acid position corresponding to position 317. Petition 870260056387, dated 10 / 06 / 2026, page 52 / 926 44 / 305 318, an arginine residue (R) at the amino acid position corresponding to position 326, a tyrosine residue (Y) at the amino acid position corresponding to position 338, a glycine residue (G) at the amino acid position corresponding to position 363, and an alanine residue (A) at the amino acid position corresponding to position 372, wherein the position numbers are with reference to SEQ ID NO:41. In some embodiments, the methods involve administering to the individual a therapeutically effective amount of one or more immunogenic compositions comprising a mixture comprising a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of any of the SEQ ID NOs: 27 to 32 and 89 to 94, for example, SEQ ID NOs: 29, 89, 90 or 92, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 27 to 32 and 89 to 94, for example, SEQ ID NOs: 29, 89, 90 or 92; (b) the second viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of any of the SEQ ID NOs: 33 to 37, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 33 to 37. In some embodiments, the methods comprise administering to the individual a therapeutically effective amount of one or more immunogenic compositions comprising a mixture comprising a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence nucleic acid of SEQ ID NO: 29 or, Petition 870260056387, dated 10 / 06 / 2026, p. 53 / 926 45 / 305 90, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 29 or 90; (b) the second viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 37, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37. In some embodiments of the methods, the first viral expression vector and the second viral expression vector are Arenaviridae.In some embodiments of the methods, the first viral expression vector and the second viral expression vector are arenavirus vectors selected from lymphocytic choriomeningitis mamarenavirus (LCMV), Cali mamarenavirus (also called Pichindé mamarenavirus or Pichindé arenavirus (PICV)), Guanarito virus (GTOV), Junín virus (JUNV), Lassa virus (LASV), Lujo virus (LUJV), Machupo virus (MACV), Sabiá virus (SABV), and Whitewater Arroyo virus (WWAV). In some embodiments of the methods, the first viral expression vector and the second viral expression vector are arenavirus vectors selected from lymphocytic choriomeningitis mamarenavirus (LCMV) or Cali mamarenavirus (also called Pichindé mamarenavirus or Pichindé arenavirus (PICV)). In some embodiments of the methods, the first viral expression vector and the second viral expression vector are replication-defective or replication-deficient.In some embodiments of the methods, the first viral expression vector and the second viral expression vector are attenuated for replication. In some embodiments, the methods comprise administering to the individual a therapeutically effective amount of one or more immunogenic compositions comprising a mixture comprising a first LCMV arenavirus expression vector and a second viral expression vector. Petition 870260056387, dated 10 / 06 / 2026, page 54 / 926 46 / 305 second LCMV arenavirus expression vector, wherein: (a) the first LCMV arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 29, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 29; and (b) the second LCMV arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 37, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 37.In some embodiments, the methods comprise administering to the individual a therapeutically effective amount of one or more immunogenic compositions comprising a mixture comprising a first Pichindé arenavirus expression vector and a second Pichindé arenavirus expression vector, wherein: (a) the first Pichindé arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of SEQ ID NO: 90, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 90; and (b) the second Pichindé arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 37, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 37.In some of the methods, the individual is infected with HBV, is suspected of being infected with HBV, or is at risk of being infected with HBV. In some of the methods, the individual is asymptomatic. Petition 870260056387, dated 10 / 06 / 2026, p. 55 / 926 47 / 305 In some method modalities, the individual is chronically infected with HBV. In some method modalities, the individual is presenting or experiencing one or more selected symptoms from liver failure, liver cancer, liver fibrosis, and liver cirrhosis. In some method modalities, the individual is acutely infected with HBV. In some method modalities, the individual is presenting or experiencing one or more selected symptoms from jaundice, visible networks of dilated blood vessels in the skin, dark-colored urine (e.g., orange or brown), light-colored stools, fever, persistent fatigue, malaise, abdominal pain, abdominal fluid, loss of appetite, nausea, and vomiting. In some method modalities, the individual is co-infected with hepatitis D virus (HDV).In some embodiments of the methods, the composition is administered via a selected route from intravenous, intramuscular, intradermal, subcutaneous, and mucosal (e.g., buccal, intranasal, intrarectal, intravaginal). In some embodiments, the methods involve administering to the individual approximately 10³ to approximately 10¹² viral focus-forming units (FFUs) or plaque-forming units (PFUs) or infectious units (IU) or viral particles (VPs), for example, approximately 10⁴ to approximately 10⁷ viral FFUs or PFUs or IUs or VPs, for example, approximately 10³ to approximately 10⁴, 10⁵, 10⁶, 10⁷, 10⁸, 10⁹, 10¹⁰, 10¹¹ or 10¹² viral FFUs or PFUs or IUs or VPs, per administration. In some embodiments of the methods, one or more compositions are administered multiple times. In some modalities, the methods involve administering intravenously or intramuscularly approximately 10⁶ to approximately 10⁸ UFF or UFP or IU viral or pv per administration every two weeks (Q2W) or monthly (Q4W).In some modalities, the methods involve multiple administrations of one or more immunogenic compositions over a period of at least approximately 2 weeks. Petition 870260056387, dated 10 / 06 / 2026, p. 56 / 926 48 / 305 months at 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, or more, or until sAg is no longer detectable in the individual's serum or plasma. In some embodiments, the methods comprise a sensitization-booster regimen comprising administering a sensitization composition at a first time point and administering one or more booster compositions at one or more subsequent time points. As appropriate, the methods may involve repeating the sensitization-booster regimen in one or more iterations. In some modalities of the methods, the administrations of the sensitization composition and one or more booster compositions are spaced at least 1 week apart and up to at least 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months or 6 months apart.In some embodiments of the methods, the sensitization composition and the booster composition may comprise the same immunogenic composition or may comprise different immunogenic compositions. In some embodiments of the methods, the sensitization composition and the booster composition comprise the same one or more polypeptides and the same viral expression vector. In some embodiments of the methods, the sensitization composition and the booster composition comprise different polypeptides and / or different viral expression vectors. In some embodiments, the methods involve sensitizing with a sensitization composition comprising one or more (e.g., first and second) viral expression vectors, and boosting with a booster composition comprising one or more (e.g., third and fourth) viral expression vectors. In several embodiments, the sensitization-booster regimen comprises: (a). Petition 870260056387, dated 10 / 06 / 2026, page 57 / 926 49 / 305 (a) Sensitizing with a sensitization composition comprising one or more viral expression vectors and reinforcing with a booster composition comprising one or more polynucleotides, wherein the one or more polynucleotides comprise self-replicating DNA, cDNA, mRNA, or RNA; (b) Sensitizing with a sensitization composition comprising one or more polynucleotides, wherein the one or more polynucleotides comprise self-replicating DNA, cDNA, mRNA, or RNA, and reinforcing with a booster composition comprising one or more viral expression vectors; (c) Sensitizing with a sensitization composition comprising one or more viral expression vectors and reinforcing with a booster composition comprising one or more viral expression vectors, wherein the one or more viral expression vectors in the sensitization composition and the one or more viral expression vectors in the booster composition are from identical, related, or unrelated taxonomic families;(d) Sensitizing with a sensitizing composition comprising one or more replication-deficient viral expression vectors, and boosting with a booster composition comprising one or more replication-deficient viral expression vectors, wherein the one or more replication-deficient viral expression vectors in the sensitizing composition and the one or more replication-deficient viral expression vectors in the booster composition are from identical, related or unrelated taxonomic families; (e) Sensitizing with a sensitizing composition comprising one or more replication-attenuated viral expression vectors, and boosting with a booster composition comprising one or more replication-attenuated viral expression vectors, wherein the one or more replication-attenuated viral expression vectors in the sensitizing composition and the one or more replication-attenuated viral expression vectors in the booster composition are from identical taxonomic families; Petition 870260056387, dated 10 / 06 / 2026, p. 58 / 926 50 / 305 boosters are from identical taxonomic families, related or unrelated; (f) Sensitize with a sensitization composition comprising one or more replication-deficient viral expression vectors and boost with a booster composition comprising one or more replication-attenuated viral expression vectors; (g) Sensitize with a sensitization composition comprising one or more replication-attenuated viral expression vectors and boost with a booster composition comprising one or more replication-deficient viral expression vectors; (h) Sensitize with a sensitization composition comprising one or more lymphocytic choriomeningitis mamarenavirus (LCMV) viral expression vectors and boost with a booster composition comprising one or more Pichindé mamarenavirus (PICV) viral expression vectors;(i) Sensitizing with a sensitizing composition comprising one or more viral expression vectors of Pichindé mamarenavirus (PICV) and boosting with a booster composition comprising one or more viral expression vectors of lymphocytic choriomeningitis mamarenavirus (LCMV); (j) Sensitizing with a sensitizing composition comprising one or more viral expression vectors of Pichindé mamarenavirus (PICV) deficient in replication and boosting with a booster composition comprising one or more viral expression vectors of lymphocytic choriomeningitis mamarenavirus (LCMV) deficient in replication; (k) Sensitizing with a sensitizing composition comprising one or more viral expression vectors of lymphocytic choriomeningitis mamarenavirus (LCMV) deficient in replication and boosting with a booster composition comprising one or more viral expression vectors of Pichindé mamarenavirus (PICV) deficient in replication;(l) To raise awareness with a sensitization composition comprising one or more viral expression vectors of; Petition 870260056387, dated 10 / 06 / 2026, page 59 / 926 51 / 305 arenavirus and booster with a booster composition comprising one or more adenovirus viral expression vectors; (m) Sensitize with a sensitization composition comprising one or more adenovirus viral expression vectors and booster with a booster composition comprising one or more arenavirus viral expression vectors; (n) Sensitize with a sensitization composition comprising one or more poxvirus viral expression vectors and booster with a booster composition comprising one or more arenavirus viral expression vectors; (o) Sensitize with a sensitization composition comprising one or more arenavirus viral expression vectors and booster with a booster composition comprising one or more poxvirus viral expression vectors;(p) Sensitizing with a sensitizing composition comprising one or more poxvirus viral expression vectors and boosting with a booster composition comprising one or more adenovirus viral expression vectors; or (q) Sensitizing with a sensitizing composition comprising one or more adenovirus viral expression vectors and boosting with a booster composition comprising one or more poxvirus viral expression vectors. In some embodiments, the methods involve a sensitization-booster regimen comprising: (a) Sensitizing with a sensitizing composition comprising one or more lymphocytic choriomeningitis mamarenavirus (LCMV) viral expression vectors and boosting with a booster composition comprising one or more Pichindé mamarenavirus (PICV) viral expression vectors;(b) Sensitize with a sensitization composition comprising one or more viral expression vectors of Pichindé mamarenavirus (PICV) and boost with a booster composition comprising one or more viral expression vectors of lymphocytic choriomeningitis mamarenavirus (LCMV); (c) Sen; Petition 870260056387, dated 10 / 06 / 2026, page 60 / 926 52 / 305 sensitize with a sensitizing composition comprising one or more replication-deficient Pichindé mamarenavirus (PICV) viral expression vectors and boost with a booster composition comprising one or more replication-deficient lymphocytic choriomeningitis mamarenavirus (LCMV) viral expression vectors; or (d) Sensitize with a sensitizing composition comprising one or more replication-deficient lymphocytic choriomeningitis mamarenavirus (LCMV) viral expression vectors and boost with a booster composition comprising one or more replication-deficient Pichindé mamarenavirus (PICV) viral expression vectors. In some embodiments, the sensitizing composition and the booster composition comprise an immunogenic composition as described herein.In some embodiments, the individual is not receiving antiviral therapy or the antiviral therapy is discontinued before the administration of one or more immunogenic compositions. In some embodiments of the methods, antiviral therapy is discontinued after one or more administrations of one or more immunogenic compositions. In some embodiments, the methods additionally comprise administering to the individual one or more additional therapeutic agents, for example, two, three, four, or more additional therapeutic agents. In some embodiments, the methods comprise co-administering one or more agonists or activators of one or more Toll-like receptors (TLRs). In some embodiments, the methods comprise co-administering one or more TLR agonists or activators selected from among a TLR2 agonist, a TLR3 agonist, a TLR4 agonist, a TLR5 agonist, a TLR7 agonist, a TLR8 agonist, and a TLR9 agonist.In some modalities, the methods involve co-administering a TLR7 agonist selected from GS-9620 (vesatolimod), R848 (resiquimod), DS-0509, LHC-165, and TMX-101 (imiquimod). Petition 870260056387, dated 10 / 06 / 2026, page 61 / 926 53 / 305 In some embodiments, the methods involve co-administering a TLR8 agonist selected from GS-9688, R848 (resiquimod), and NKTR262 (dual TLR7 / TLR8 agonist). In some embodiments, the methods involve co-administering one or more interleukin receptor agonists selected from IL-2, IL-7, IL-12, and IL-15. In some embodiments, the methods involve co-administering one or more cytokines selected from IL-2, IL-7, IL-12, IL-15, and variants thereof. In some embodiments, the methods involve co-administering one or more innate immune activators. In some embodiments, the methods involve co-administering one or more innate immune activators comprising an agonist of a receptor selected from among fms-related tyrosine kinase 3 (FLT3), receptor stimulator of interferon genes (STING), DExD / H-box helicase 58 (DDX58; also called RIGI), protein containing nucleotide-binding oligomerization domain 2 (NOD2).In some embodiments, the methods involve co-administering GS-3583 and / or GS-9992. In some embodiments, the methods involve co-administering one or more inhibitory antagonists or inhibitors of an immune checkpoint receptor or protein and / or one or more activators or agonists of an immune checkpoint receptor or protein. In some embodiments, the methods involve co-administering one or more of the following immune checkpoint receptors or proteins: CD27, CD70; CD40, CD40LG; CD47, CD48 (SLAMF2), transmembrane domain-containing immunoglobulin protein 2 (TMIGD2, CD28H), CD84 (LY9B, SLAMF5), CD96, CD160, MS4A1 (CD20), CD244 (SLAMF4); CD276 (B7H3); V-set domain containing T cell activation inhibitor 1 (VTCN1, B7H4); immunoregulatory receptor with V-Set domain (VSIR, B7H5, VISTA); immunoglobulin superfamily member 11 (IGSF11, VSIG3); cytotoxic receptor ligand 1. Petition 870260056387, dated 10 / 06 / 2026, p. 62 / 926 54 / 305 natural killer cell city 3 (NCR3LG1, B7H6); HERV-H LTR-associated protein 2 (HHLA2, B7H7); inducible T-cell co-stimulator (ICOS, CD278); inducible T-cell co-stimulator ligand (ICOSLG, B7H2); member 4 of the TNF receptor superfamily (TNFRSF4, OX40); member 4 of the TNF superfamily (TNFSF4, OX40L); TNFRSF8 (CD30), TNFSF8 (CD30L); TNFRSF10A (CD261, DR4, TRAILR1), TNFRSF9 (CD137), TNFSF9 (CD137L); TNFRSF10B (CD262, DR5, TRAILR2), TNFRSF10 (TRAIL); TNFRSF14 (HVEM, CD270), TNFSF14 (HVEML); CD272 (associated with B and T lymphocytes (BTLA)); TNFRSF17 (BCMA, CD269), TNFSF13B (BAFF); TNFRSF18 (GITR), TNFSF18 (GITRL); MHC class I polypeptide-related sequence A (MICA); MHC class I polypeptide-related sequence B (MICB); CD274 (CD274, PDL1, PD-L1); programmed cell death 1 (PDCD1, PD1, PD-1); T lymphocyte-associated cytotoxic protein 4 (CTLA4, CD152); CD80 (B7-1), CD28; nectin cell adhesion molecule 2 (NECTIN2, CD112);CD226 (DNAM-1); poliovirus receptor (PVR) cell adhesion molecule (PVR, CD155); PVR-related immunoglobulin domain-containing protein (PVRIG, CD112R); T-cell immunoreceptor with Ig and ITIM domains (TIGIT); T-cell immunoglobulin-containing mucin domain protein 4 (TIMD4; TIM4); hepatitis A virus cell receptor 2 (HAVCR2, TIMD3, TIM3); galectin 9 (LGALS9); lymphocyte activation 3 (LAG3, CD223); lymphocyte activation molecule signaling family member 1 (SLAMF1, SLAM, CD150); lymphocyte antigen 9 (LY9, CD229, SLAMF3); SLAM family member 6 (SLAMF6, CD352); SLAM family member 7 (SLAMF7, CD319); UL16-binding protein 1 (ULBP1); UL16-binding protein 2 (ULBP2); UL16-binding protein 3 (ULBP3); early transcription of retinoic acid 1E (RAET1E; ULBP4); early transcription of retinoic acid 1G (RAET1G; ULBP5); early transcription of retinoic acid; Petition 870260056387, dated 10 / 06 / 2026, page 63 / 926 55 / 305 1L (RAET1L; ULBP6); lymphocyte activator gene 3 (CD223); killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR, CD158E1); killer cell lectin-like receptor C1 (KLRC1, NKG2A, CD159A); killer cell lectin-like receptor K1 (KLRK1, NKG2D, CD314); killer cell lectin-like receptor C2 (KLRC2, CD159c, NKG2C); killer cell lectin-like receptor C3 (KLRC3, NKG2E); killer cell lectin-like receptor C4 (KLRC4, NKG2F); killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 1 (KIR2DL1); Killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 2 (KIR2DL2); Killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 3 (KIR2DL3);Killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR3DL1); killer cell lectin-like receptor D1 (KLRD1); SLAM family member 7 (SLAMF7). In some embodiments, the methods involve co-administering one or more blockers or inhibitors of one or more T cell inhibitory immune checkpoint receptors or proteins. In some embodiments, the methods involve co-administering one or more T cell inhibitory immune checkpoint receptors or proteins selected from CD274 (CD274, PDL1, PD-L1); programmed cell death ligand 1 (PDCD1LG2, PD-L2, CD273); programmed cell death 1 (PDCD1, PD1, PD-1); T lymphocyte-associated cytotoxic protein 4 (CTLA4, CD152); CD276 (B7H3); V-set domain containing T cell activation inhibitor 1 (VTCN1, B7H4); immunoregulatory receptor with V-Set domain (VSIR, B7H5, VISTA);immunoglobulin superfamily member 11 (IGSF11, VSIG3); TNFRSF14 (HVEM, CD270),; Petition 870260056387, dated 10 / 06 / 2026, page 64 / 926 56 / 305 TNFSF14 (HVEML); CD272 (associated with B and T lymphocytes (BTLA)); containing PVR-related immunoglobulin domain (PVRIG, CD112R); T-cell immunoreceptor with Ig and ITIM domains (TIGIT); lymphocyte activation 3 (LAG3, CD223); hepatitis A virus cell receptor 2 (HAVCR2, TIMD3, TIM3); galectin 9 (LGALS9); killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR, CD158E1); killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 1 (KIR2DL1); killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 2 (KIR2DL2); Killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 3 (KIR2DL3); and killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR3DL1).In some embodiments, the methods involve co-administering one or more agonists or activators of one or more T-cell stimulating immune checkpoint receptors or proteins. In some embodiments, the methods involve co-administering one or more T-cell stimulating immune checkpoint receptors or proteins selected from CD27, CD70; CD40, CD40LG; inducible T-cell costimulator (ICOS, CD278); inducible T-cell costimulator ligand (ICOSLG, B7H2); TNF receptor superfamily member 4 (TNFRSF4, OX40); TNF superfamily member 4 (TNFRSF4, OX40L); TNFRSF9 (CD137), TNFSF9 (CD137L); TNFRSF18 (GITR), TNFSF18 (GITRL); CD80 (B7-1), CD28; Nectin cell adhesion molecule 2 (NECTIN2, CD112); CD226 (DNAM-1); poliovirus receptor (PVR) cell adhesion molecule (PVR, CD155). In some embodiments, the methods involve co-administering AGEN-2373 and / or AGEN-1223.In some modalities, the methods involve co-administering one or more blocked Petition 870260056387, dated 10 / 06 / 2026, page 65 / 926. 57 / 305 inhibitors of one or more immune checkpoint receptors or proteins, NK cell inhibitors.In some embodiments, the methods involve co-administering one or more selected NK cell inhibitory immune checkpoint receptors or proteins from among killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR, CD158E1); killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 1 (KIR2DL1); killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 2 (KIR2DL2); killer cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 3 (KIR2DL3); killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR3DL1); killer cell lectin-like C1 receptor (KLRC1, NKG2A, CD159A); and killer cell lectin-like D1 receptor (KLRD1, CD94).In some embodiments, the methods involve co-administering one or more agonists or activators of one or more NK cell-stimulating immune checkpoint receptors or proteins. In some embodiments, the methods involve co-administering one or more NK cell-stimulating immune checkpoint receptors or proteins selected from CD16, CD226 (DNAM-1); killer cell lectin-like K1 receptor (KLRK1, NKG2D, CD314); SLAM family member 7 (SLAMF7). In some embodiments, the methods involve co-administering one or more PD-L1 (CD274), PD-1 (PDCD1), or CTLA4 proteinaceous inhibitors. In some embodiments, the methods involve co-administering one or more CTLA4 proteinaceous inhibitors selected from ipilimumab, tremelimumab, BMS-986218, AGEN1181, AGEN1884, BMS-986249. MK-1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JSPetição 870260056387, dated 10 / 06 / 2026, page 66 / 926 58 / 305 007, BA-3071, ONC-392, AGEN-2041, JHL-1155, KN-044, CG-0161, ATOR-1144, PBI-5D3H5, FPT-155 (CTLA4 / PD-L1 / CD28), PF0693630 (CTLA4 / PD-L1 / CD28), MG-PD-199 (PD-1 / CTLA4), KN-046 (PD1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4) and AK-104 (CTLA4 / PD-1).In some embodiments, the methods involve coadministering one or more proteinase inhibitors of PD-L1 (CD274) or PD-1 (PDCD1) selected from zimberelimabe (AB122), pembrolizumabe, nivolumabe, cemiplimabe, pidilizumabe, AMP-224, MEDI0680 (AMP-514), spartalizumab, atezolizumab, avelumab, ASC22, durvalumab, BMS-936559, CK-301, PF-06801591, BGB-A317 (tislelizumab), GLS-010 (WBP-3055), AK-103 (HX-008), AK-105, CS-1003, HLX-10, MGA-012, BI-754091, AGEN-2034, JS-001 (toripalimabe), JNJ-63723283, genolimzumab (CBT-501), LZM-009, BCD-100, LY-3300054, SHR-1201, SHR-1210 (camrelizumab), Sym021, ABBV-181, PD1-PIK, BAT-1306, (MSB0010718C), CX-072, CBT502, TSR-042 (dostarlimab), MSB-2311, JTX-4014, BGB-A333, SHR1316, CS-1001 (WBP-3155, KN-035, IBI-308 (cylindrical), HLX-20,. KL-A167, STI-A1014, STI-A1015 (IMC-001), BCD-135, FAZ-053, TQB2450, MDX1105-01, FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-013 (PD-1 / LAG-3), FS-118 (LAG-3 / PD-L1) MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), RO-7121661 (PD-1 / TIM-3), (CTLA4 / PD-1), M7824 (EC domain of PDL1 / TGFP), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY3415244 (TIM3 / PDL1), and INBRX-105 (4-1BB / PDL1). In some embodiments, the method involves co-administering one or more small molecule inhibitors of CD274 (PDL1, PD-L1), programmed cell death 1 (PDCD1, PD1, PD-1), or CTLA4. In some embodiments, the methods involve co-administering one or more small molecule inhibitors of CD274 or PDCD1 selected from GS-4224, GS Petition 870260056387, dated 10 / 06 / 2026, page 67 / 926 59 / 305 4416, INCB086550 and MAX10181. In some embodiments, the methods involve co-administering BPI-002 (a small molecule inhibitor of CTLA4). In some embodiments, the methods comprise co-administering to the individual one or more antiviral agents. In some embodiments, the methods comprise co-administering one or more antiviral agents selected from lamivudine (LAM), adefovir dipivoxil (ADV), entecavir (ETV), telbivudine (LdT), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF or VEMLIDY®) and ledipasvir + sofosbuvir (HARVONI®).In some embodiments, the methods comprise co-administering to the individual one or more therapeutic agents selected from among HBV antigen inhibitors (e.g., HBV core antigen inhibitors (HBcAg), HBV surface antigen inhibitors (HBsAg), HBx inhibitors, HBV E antigen inhibitors), anti-HBV antigen antibodies, HBV-targeted inhibitory nucleic acids (e.g., antisense oligonucleotide, short interfering RNA (siRNA), DNA-targeted interfering RNA (ddRNAi)), HBV-targeted gene editors (e.g., CRISPR-Cas (e.g., Cas9, Cas12, Cascade, Cas13), zinc finger nucleases, guided endonucleases, guided meganucleases (e.g., ARCUS), synthetic nucleases, TALENs), covalently closed circular DNA (cccDNA) inhibitors, and secretion or assembly inhibitors of HBsAg and HBV viral entry inhibitors.In some modalities, the method activates CD8+ T cells and / or CD4+ T cells in the individual that target one or more HBV polypeptide epitopes. In some modalities, the method elicits the production of antibodies in the individual that bind to one or more HBV polypeptides. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 illustrates the immunogenicity of adenoviral vectors expressing HBsAg of genotypes (GT) A, B, C and D in ca Petition 870260056387, dated 10 / 06 / 2026, p. 68 / 926 60 / 305 DO mice. In heterogeneous (Diversity Outbred (DO)) mice aged five to seven weeks (n = 8 per group), 1 x 10⁸ adenovirus viral particles (vp) encoding HBsAg consensus sequences of HBV genotypes (GT) A, B, C, D (SEQ ID NOs: 1 to 4, respectively) were injected intramuscularly. On day 14 after injection, splenocytes were harvested and T cell responses were assessed by ELISPOT of (IFN)-γ (BD mouse ELISPOT IFN-γ kit, catalog number 551083). Each symbol corresponds to an individual mouse that was evaluated for responses to overlapping peptide pools corresponding to HBsAg of GT-A, B, C, and D.

[0020] Figure 2 illustrates schematics of each Pol-containing antigen design. Each Pol domain is indicated separately (TP, terminal protein; RT, reverse transcriptase; RNH, RNase H). The approximate location of the D to H mutation in the YMDD motif (SEQ ID NO: 97) in RT and the E to H mutation in the AELL motif (SEQ ID NO: 98) in RNH are indicated below the RT and RNH domains. The designation of each construct is shown on the left, and the amino acid size range of the GT-A, B, C, and D constructs is shown on the right. YMHD and AHLL are revealed as SEQ ID NOs: 99 and 100, respectively.

[0021] Figure 3 illustrates the immunogenicity of adenoviral vectors expressing nucleus-Pol fusion protein in C57BL / 6 mice. In six- to eight-week-old C57BL / 6 mice (n = 5 per group), 1 x 10⁸ adenovirus viral particles (vp) encoding nucleus-Pol fusion variants of SEQ ID NOs 15 to 26 were injected. The genotype of each antigen is shown above each graph, while the antigen designations are shown on the horizontal axis (Mut: nucleus-Polmut, Δ1: nucleus-PolA1, Δ3: nucleus-PoP3). On day 14 after injection, splenocytes were harvested and T cell responses were Petition 870260056387, dated 10 / 06 / 2026, page 69 / 926 61 / 305 evaluated by IFN-γ ELISPOT (BD mouse ELISPOT IFN-γ kit, catalog number 551083) using overlapping peptide pools corresponding to core and GT-D Pol. Bars show pooled geometric mean responses for each group. SFU, spot-forming units.

[0022] Figures 4A to 4B illustrate the immunogenicity of adenoviral vectors expressing nucleus fusion protein Pol in DO mice. In DO mice aged five to seven weeks (n = 8 per group), 1 x 10⁸ viral particles (vp) of adenovirus encoding nucleus-PoP3 of GTA or nucleus-PoP1 of GT-B, C, or D were injected intramuscularly. On day 14 after injection, splenocytes were harvested and T cell responses were assessed by IFN-γ ELISPOT (BD mouse ELISPOT IFN-γ kit, catalog number 551083) for overlapping peptide pools corresponding to nucleus and Pol of GT-A and D. Statistical comparisons between responses to peptides from different mouse genotypes that received the same vaccine were evaluated using Wilcoxon signed-rank tests. Statistical comparisons between mice that received different vaccines were evaluated using Mann-Whitney tests. (A) Responses to Pol peptides.(B) Responses to core peptides. SFU, spot-forming units.

[0023] Figure 5 illustrates the immunogenicity of adenoviral vectors expressing Pol. In six- to eight-week-old C57BL / 6 mice (n = 5 per group), 1 x 10⁸ adenovirus viral particles (vp) expressing Pol antigen variants of SEQ ID NOs: 8, 12, 13, 14 or an entire GT-D Pol sequence (GT-D PolControl) were injected. On day 14 after injection, splenocytes were harvested and T cell responses were assessed by IFN-γ ELISPOT (BD mouse ELISPOT IFN-γ kit, catalog number 551083) using overlapping peptide pools. Petition 870260056387, dated 10 / 06 / 2026, page 70 / 926 62 / 305 Pol de GT-D. SFU: spot forming units.

[0024] Figure 6 illustrates the study design evaluating the efficacy of Ad5 and vaccinia vectors expressing HBV in the AAV mouse model of HBV-associated cholera (AAV-HBV). Six- to eight-week-old C57BL / 6 mice were transduced with 1012 copies of the AAV-HBV genome on day 35. Mice were randomized to treatment groups based on serum HBsAg levels on day 7. Adenovirus type 5 sensitization vaccines expressing HBV antigens were administered intramuscularly (im) at 50 μl on day 0, and vaccinia booster vaccines expressing the same HBV antigens were administered im at 50 μl on day 32. From days 46 to 67, mice received both RMP 1-14 anti-PD-1 (anti-CD279) monoclonal antibody and isotype control mAb. Blood samples were collected for viral antigen testing on days 7, 14, 27, 46, 60, 67, and 88. Splenocytes were collected on day 88 and evaluated by IFN-γ ELISPOT.

[0025] Figure 7 illustrates the immunogenicity of Ad5-booster vaccinia sensitization vaccination in AAV-HBV mice. Splenocytes were harvested on day 88 in the study shown in Figure 6. T cell responses to HBsAg and Pol were assessed by IFN-γ ELISPOT (BD mouse ELISPOT IFN-γ kit, catalog number 551083) using overlapping peptide pools corresponding to GT-D sAg and Pol. The dashed line indicates the highest signal on the HBsAg ELISPOT observed in mice receiving the control vaccine. mAb: administered monoclonal antibody. Iso: isotype control. αPD-1: anti-PD-1. Vax: indicates whether the vaccine contained HBV antigens or control antigens (Control). SFU: spot-forming units.

[0026] Figure 8 illustrates the effects of sensitization vaccination with Ad5-booster with vaccinia expressing HBV in combination with Petition 870260056387, dated 10 / 06 / 2026, page 71 / 926 63 / 305 PD-1 blockade in AAV-HBV mice. Serum HBeAg levels in the study shown in Figure 6 were determined by ELISA (International Immunodiagnostics) at the indicated time points. The dashed line indicates the lower limit of detection. Ad: adenoviral vector 5. Vac: vaccinia vector. Control: control antigen. Isotype: isotype control antibody. aPD-1: mouse anti-PD-1 antibody.

[0027] Figures 9A to 9C illustrate an overview of the arenavirus vector platforms demonstrated in the examples provided here. (A) Schematic of a phylogenetic tree of the arenavirus family (Arenaviridae). In the examples provided here, lymphocytic choriomeningitis mamarenavirus (LCMV)(NCBI:txid11623), from the Old World (OW) clade, and Cali mamarenavirus (also called Pichindé mamarenavirus or Pichindé arenavirus (PICV))(NCBI:txid2169993) from the New World (NW) clade were selected for generating vectors encoding HBV antigen. See, for example, Buchmeier et al., 2001, Arenaviridae: The Viruses and Their Replication, Fields Virology Volume 2, 1635-1668. The taxonomy of arenaviruses has been most recently revised in, for example, Radoshitzky, et al., Arch Virol. (2015) 160(7):1851-74. Phylogenetic information for Arenaviridae is also available on the Virus Pathogen Resource website, located at viprbrc.org. (B) Schematic of replication-defective arenavirus vectors having a bisegmented genome, described in document WO2009083210, and (C) attenuated replication-defective arenavirus vectors having a trisegmented genome, described in documents WO2016075250 and WO2017198726. The replication-defective arenavirus vectors having a bisegmented genome, described in document WO2009083210 and used in the Examples provided here, encode three of the four viral proteins (L, Z, and NP) and an open reading frame for the insertion of a heterologous polynucleotide, for example, encoding an antigen. The arenavirus vectors Petition 870260056387, dated 10 / 06 / 2026, page 72 / 926 64 / 305 defective vectors for replication that have a bisegmented genome can only propagate when the viral GP is released trans. Attenuated arenavirus vectors for replication that have a trisegmented genome, described in documents WO2016075250 and WO2017198726, have a duplication of the S genomic segment, encode all four viral proteins (L, Z, NP, and GP), and have two open reading frames for the insertion of one or two heterologous polynucleotides, for example, encoding one or two antigens.

[0028] Figure 10 illustrates the immunogenicity of Pol antigens in replication-incompetent lymphocytic choriomeningitis (LCMV) mamarenavirus vectors. In six- to eight-week-old C57BL / 6 mice (n = 6 per group), 1 x 10⁶ focus-forming units (FFU) of replication-incompetent LCMV vectors expressing Pol antigen variants GT-D and GTB ΡοΙΔ1 (SEQ ID NOs: 6 and 8), ΡοΙΔ3 (SEQ ID NOs: 10 and 12), and Pol300 (SEQ ID NOs: 13 and 14) were injected intravenously, or with medium as a negative control. On day 7 after injection, splenocytes were collected and T cell responses were assessed by IFN-γ ELISPOT (BD mouse ELISPOT IFN-γ kit, catalog number 551083) using overlapping Pol peptide pools corresponding to the immunization antigen genotype in each group. SFU, spot-forming units.

[0029] Figure 11 illustrates the immunogenicity of LCMV vectors expressing HBsAg-nucleus fusion protein in C57BL / 6 mice. In six- to eight-week-old C57BL / 6 mice (n = 6 per group), 1 x 10⁶ focus-forming units (FFUs) of replication-incompetent LCMV vectors expressing HBsAg-nucleus fusion variants of SEQ ID NOs 38 to 41 were injected, or sham immunized mice were used as a negative control. On day 7 after injection, splenocytes were collected and T-cell responses were assessed by IFN-γ ELISPOT (IFN-γ ELISPOT kit). Petition 870260056387, dated 10 / 06 / 2026, page 73 / 926 65 / 305 mouse BD, catalog number 551083) using overlapping core peptide pools and HBsAg corresponding to the immunization antigen genotype in each group. SFU, spot-forming units.

[0030] Figure 12 illustrates the antibody response to HBsAg obtained in mice administered replication-incompetent LCMV vectors expressing nucleo-fusion protein sAg. In six- to eight-week-old C57BL / 6 mice (left) or Balb / c mice (right) (n = 5 per group), 1 x 10⁶ focus-forming units (FFU) of replication-incompetent LCMV vectors expressing nucleo-fusion variants of SEQ ID NOs 38 to 41 were injected, or with medium as a negative control. On day 17 after injection, serum was collected and tested for anti-HBsAg antibody by ELISA (International Immunodiagnostics). The dashed line indicates the lower limit of detection of 11 mIU / ml. *p < 0.05 by Mann-Whitney test.

[0031] Figure 13 illustrates the effect of nucleotide sequence modification on the T cell immunogenicity of nucleus-P2A-sAg fusion proteins. In six- to eight-week-old C57BL / 6 mice (n = 6 per group), 1 x 106 focus-forming units (FFU) of replication-incompetent LCMV vectors with GT-D nucleus-P2A-sAg (SEQ ID NO:36) or GT-D iNucleus-P2A-sAg (SEQ ID NO: 37) were injected, or immunized in sham as a negative control. On day 7 after injection, splenocytes were harvested and T cell responses were assessed by IFN-γ ELISPOT (BD mouse ELISPOT IFN-γ kit, catalog number 551083) using overlapping nucleolus and sAg peptide pools. Statistical analyses were performed using Mann-Whitney tests.

[0032] Figures 14A to 14B illustrate the immunogenicity of sensitization / booster vaccination with incompetent LCMV vectors. Petition 870260056387, dated 10 / 06 / 2026, page 74 / 926 66 / 305 for replication (VV1) encoding GT-B / C Nucleus-P2A-sAg or GTD iNucleus-P2A-sAg (Figure 14A) and GT-B Pol300 or GT-B Pol300 (Figure 14B) in heterogeneous mice. Two doses of each vaccine were administered to the animals on day 0 and day 28, as described in Table 9. Splenocytes were collected on day 42 and T cell responses to HBV antigens were measured by IFN-γ ELISPOT using sAg, nucleus, and polymerase peptide pools of various viral genotypes as indicated. Data are expressed as background-subtracted values ​​(without peptide). Statistical analyses were performed using Mann-Whitney tests. ns: not statistically significant; *p < 0.0332.

[0033] Figures 15A to 15B illustrate the range of HBV-specific T cell responses generated by sensitization / booster vaccination with replication-incompetent LCMV vectors (VV1) encoding GT-D iNucleus-P2A-sAg (Figure 15A) or GT-B Pol300 (Figure 15B) in heterogeneous mice. IFN-γ ELISPOT was performed using peptides of the same viral genotype (filled circles) or a different viral genotype (open circles).

[0034] Figures 16A to 16B illustrate the immunogenicity of sensitization / booster vaccination with replication-incompetent LCMV vectors (VV1) encoding GT-D iNucleus-P2A-sAg and GT-B Pol300 when released as single vectors or as a co-formulated mixture in C57BL / 6 mice. Two doses of the vectors were administered to the animals on day 0 and day 21, as described in Table 10. Splenocytes were harvested on day 28 and HBV-specific T cell responses were measured by IFNγ ELISPOT using nucleus (16A), sAg (16B), and Pol (16C) peptide pools.

[0035] Figures 17A to 17F illustrate the immunogenicity of repeated vaccinations with LCMV vectors incompetent for replication. Petition 870260056387, dated 10 / 06 / 2026, page 75 / 926 67 / 305 encoding GT-D iNucleus-P2A-sAg and GT-B Pol300 in cynomolgus monkeys. A group of animals was also vaccinated with Ad5 and vaccinia vectors encoding the same HBV antigens. The vectors were administered to the animals as described in Table 11. 17A: Group 1; 17B: Group 2; 17C: Group 3; 17D: Group 4; 17E: Group 5; 17F: Group 6. T cell responses to HBV antigens were assessed by performing IFN-γ ELISPOT using sAg, nucleus, and Pol peptide pools at the indicated time points. The data are expressed as total HBV-specific T cell responses defined as the sum of IFN-γ ELISPOT values ​​obtained after stimulation with sAg, nucleus, and polymerase peptide pools.

[0036] Figures 18A to 18F illustrate the immunogenicity of repeated vaccinations with replication-incompetent LCMV vectors encoding GT-D iNucleus-P2A-sAg and GT-B Pol300 in cynomolgus monkeys, as described in Figure 17 and Table 11. Figures 18A to 18F focus on the IFN-γ ELISPOT obtained after stimulation with core peptide pools. 18A: Group 1; 18B: Group 2; 18C: Group 3; 18D: Group 4; 18E: Group 5; 18F: Group 6.

[0037] Figures 19A to 19F illustrate the immunogenicity of repeated vaccinations with replication-incompetent LCMV vectors encoding GT-D iNucleus-P2A-sAg and GT-B Pol300 in cynomolgus monkeys, as described in Figure 17 and Table 11. Figures 19A to 19F focus on the IFN-γ ELISPOT obtained after stimulation with sAg peptide pools. 19A: Group 1; 19B: Group 2; 19C: Group 3; 19D: Group 4; 19E: Group 5; 19F: Group 6.

[0038] Figures 20A to 20F illustrate the immunogenicity of repeated vaccinations with replication-incompetent LCMV vectors encoding GT-D iNucleus-P2A-sAg and GT-B Pol300 in cynomolgus monkeys, as described in Figure 17 and Table 11. Petition 870260056387, dated 10 / 06 / 2026, page 76 / 926 68 / 305 ras 20A to 20F concentrate on the IFN-γ ELISPOT obtained after stimulation with sAg peptide pools. 20A: Group 1; 20B: Group 2; 20C: Group 3; 20D: Group 4; 20E: Group 5; 20F: Group 6.

[0039] Figures 21A and 21B illustrate the frequency of T cells. CD8+ (A) and CD4+ (B) HBV-specific IFN-γ T cells at week 14 in cynomolgus monkeys from groups 1, 2, and 6 as described in Table 11. Data are obtained from CMSPs harvested at week 14 and re-stimulated with peptide pools of sAg, nucleus, and HBV polymerase. CD4+ and CD8+ T subsets were then analyzed for intracellular IFN-γ by flow cytometry.

[0040] Figures 22A to 22C illustrate the antibody response to HBsAg in cynomolgus monkeys from group 1 (22A), group 2 (22B), and group 6 (22C) as described in Table 11. Serum samples were collected at the indicated time points and quantified for anti-HBsAg antibody by ELISA. The dashed line indicates the lower limit of quantification of the assay (5 mIU / mL).

[0041] Figure 23 illustrates the study design evaluating the immunogenicity of replication-incompetent LCMV vectors encoding GT-D iNucleus-P2A-sAg and GT-B Pol300 (HBV vaccine) alone or in combination with the immunomodulators anti-PD1, anti-CTLA4, anti-CD137 and FLT3L-Fc fusion in the AAVHBV mouse model. Six- to ten-week-old C57BL / 6 mice were transduced with 1011 copies of the AAV-HBV genome on day 35. Mice were randomized to treatment groups based on serum HBsAg levels on day 11. Replication-incompetent LCMV vectors encoding iNucleus-P2A-sAg and GT-B Pol300 were administered intravenously (iv) at 200 µl on days 0, 21, and 42. Mice received intraperitoneal 200 µl of i) saline solution on days 0, 7, 14, 21, 28, 35, 42, 49, and 56; ii) anti-PD-1 monoclonal antibody RMP 1-14 on days 42, 46, 49, 53, 56, and 60; iii) clone of Petition 870260056387, dated 10 / 06 / 2026, page 77 / 926 69 / 305 anti-CTLA-4 9D9 monoclonal antibody on days 0, 4, 7, 11, 14, 18, 21, 25, 28, 32, 35, 39, 42, 46, 49, and 53; iv) anti-CD137 mAb8 (IgG2b) monoclonal antibody clone on days 0, 21, and 42; v) FLT3L-Fc fusion protein on days 7, 14, and 35. The asterisks represent doses of each immunomodulator. Splenocytes were harvested on day 105 and evaluated for IFN-γ ELISPOT using sAg, nucleus, and Pol peptide pools. A group of C57BL / 6 mice that did not receive AAVHBV, but were administered replication-incompetent LCMV vectors alone, was used as a positive control for IFN-γ ELISPOT.

[0042] Figures 24A to 24C illustrate the immunogenicity of repeated vaccinations with replication-incompetent LCMV vectors encoding GT-D iNucleus-P2A-sAg and GT-B Pol300 in AAV-HBV mice as described in Table 12 and Figure 23. Splenocytes were collected on day 105 and evaluated for IFN-γ ELISPOT using peptide pools of sAg (24A), nucleus (24B), and polymerase (24C). Statistical analyses were performed using Mann-Whitney tests. ns: not statistically significant; *p < 0.0332, **p < 0.0021, ***p < 0.0002, ****p < 0.0001.

[0043] Figure 25 illustrates the immunogenicity of sensitization-booster vaccination with replication-incompetent PICV vectors (VV2) encoding GT-B Pol300ori or GT-B Pol300dint in C57BL / 6 mice. Two vaccine doses were administered to the animals on day 0 and day 21. Splenocytes were harvested on day 28 and HBV polymerase-specific T cell responses were measured by IFN-γ ELISPOT using Pol peptide pools. Data are expressed as background-subtracted values ​​(without peptide). Statistical analyses were performed using Mann-Whitney tests. **p < 0.0021.

[0044] Figures 26A to 26C illustrate the immunogenicity of vaccines Petition 870260056387, dated 10 / 06 / 2026, page 78 / 926 70 / 305 homologous and heterologous sensitization / boost with replication-incompetent LCMV (VV1) and PICV (VV2) vectors encoding GT-D iNucleus-P2A-sAg or GT-B Pol300 in C57BL / 6 mice. Twelve vector doses were administered to animals on day 0 and day 21, as described in Table 15. Splenocytes were harvested on day 28 and HBV-specific T cell responses were measured by IFN-γ ELISPOT using sAg (26A), nucleus (26B), and polymerase (26C) peptide pools. Data are expressed as background-subtracted (without peptide) values.

[0045] Figure 27 illustrates the antibody response to HBsAg in C57BL / 6 mice that received replication-incompetent LCMV and PICV vectors encoding GT-D iNucleus-P2A-sAg using homologous (VV1 / VV1) or heterologous (VV2 / VV1) sensitization / booster vaccination on day 0 and day 21. Serum samples were collected on day 21 and quantified for anti-HBsAg antibody by ELISA. The dashed line indicates the lower limit of quantification of the assay (20 mIU / mL). Statistical analyses were performed using Mann-Whitney tests. ** p < 0.0021.

[0046] Figures 28A to 28C illustrate the immunogenicity of homologous and heterologous sensitization / booster vaccination with replication-attenuated LCMV (TT1) and PICV (TT2) vectors encoding GT-D nucleus-P2A-sAg and GT-B Pol300 in C57BL / 6 mice. Two doses of the vectors were administered to the animals on day 0 and day 21, as described in Table 16. Splenocytes were harvested on day 28 and HBV-specific T cell responses were measured by IFN-γ ELISPOT using sAg (28A), nucleus (28B), and polymerase (28C) peptide pools.

[0047] Figure 29 illustrates the immunogenicity of homologous and heterologous sensitization / booster vaccination with replication-deficient LCMV (VV1) and PICV (VV2) vectors encoding GT-D nucleus-P2A. Petition 870260056387, dated 10 / 06 / 2026, p. 79 / 926 71 / 305 sAg and GT-B Pol300 in cynomolgus monkeys. Two doses of the vectors were administered to the animals, one at week 0 and one at week 4. CMSPs were collected at week 6 and HBV-specific T cell responses were measured by IFN-γ ELISPOT using sAg, core, and polymerase peptide pools. Data are expressed as total HBV-specific T cell responses defined as the sum of IFN-γ ELISPOT values ​​obtained after stimulation with sAg, core, and polymerase peptide pools. The lower limit of quantification (LLOQ) by ELISPOT (dashed line) was defined as 200 IFN-γ+ SFU / 10⁶ CMSP. Statistical analysis was performed using the Mann-Whitney test.

[0048] Figure 30 illustrates the immunogenicity of homologous and heterologous sensitization / booster vaccination with replication-deficient LCMV (VV1) and PICV (VV2) vectors encoding GT-D nucleus-P2A-sAg and GT-B Pol300 administered weekly in cynomolgus monkeys. Four doses of the vectors were administered to the animals at weeks 0, 1, 2, and 3. CMSPs were harvested at week 4, and HBV-specific T cell responses were measured by IFN-γ ELISPOT using sAg, nucleus, and polymerase peptide pools. Data are expressed as total HBV-specific T cell responses defined as the sum of IFN-γ ELISPOT values ​​obtained after stimulation with sAg, nucleus, and polymerase peptide pools. The lower limit of quantification (LLOQ) by ELISPOT (dashed line) was defined as 200 IFN-Y+ SFU / 106CMSP. DETAILED DESCRIPTION 1. Introduction

[0049] Polypeptides are provided that are useful for eliciting a protective immune response against one or more hepatitis B virus (HBV) antigens in a human. The immunogenic polypeptides described herein are capable of eliciting preventive and / or immune responses. Petition 870260056387, dated 10 / 06 / 2026, pp. 80 / 926 72 / 305 therapeutic effects in a human being against one or more hepatitis B virus (HBV) antigens. In general, the immunogenic polypeptides described herein contain highly conserved portions of HBV proteins in order to induce responses against epitopes that are identical in the vaccine antigen and in the infecting HBV present in the patient, while excluding poorly conserved regions, thus avoiding eliciting immunodominant T cell responses directed at epitopes that are not present in the patient's infecting HBV strain. The immunogenic polypeptides described herein also induce both CD4+ and CD8+ T cell responses to facilitate the elimination of infected cells, and additionally anti-sAg antibody responses that facilitate the elimination of sAg, thus reducing or eliminating residual virus propagation if viral clearance by sterilization is not completely achieved.Furthermore, the immunogenic polypeptides described herein are shown to be immunogenic when released using vaccine technologies capable of inducing the desired responses in humans, and stable in delivery vectors through sufficient vector replication cycles to allow for commercial-scale vaccine manufacture. Immunogenic polypeptides can be used in various vector systems known to induce CD4+ and CD8+ T cell and antibody responses in humans and other non-human primates. In certain embodiments, immunogenic polypeptides are expressed from arenaviral vectors that can be repeatedly dosed without inducing antivector antibodies, thus overcoming a limitation of many previous viral vector technologies and providing the possibility of increasing therapeutic benefit with repeated dosing. 2. Polypeptides useful for promoting an immune response against the hepatitis B virus (HBV)

[0050] Useful immunogenic polypeptides are provided for pro Petition 870260056387, dated 10 / 06 / 2026, page 81 / 926 73 / 305 move, induce and / or elicit an immunogenic response against one or more hepatitis B virus (HBV) antigens. In various embodiments, immunogenic polypeptides comprise variants and / or fragments of polypeptides encoded by an HBV polymerase gene (Pol) and fusion polypeptides having, in sequential order from the N-terminal to the C-terminal, a variant and / or fragment of a polypeptide encoded by an HBV core gene and a variant and / or fragment of a polypeptide encoded by the surface antigen gene (sAg). Immunogenic polypeptides may contain amino acid sequences based on consensus or near-consensus sequences of HBV genotypes A, B, C, or D, and combinations thereof. In general, the immunogenic polypeptides described herein do not comprise sequences of HBV protein X (HBx), pre-core, pre-S1, pre-S2, or fragments thereof.

[0051] In several embodiments, the immunogenic polypeptides described herein and / or the polynucleotides encoding such polypeptides are provided in isolated form. This means that such polypeptide or polynucleotide is at least 50% w / w pure from interfering proteins, cellular contaminants and other contaminants resulting from its production or purification, but does not exclude the possibility of the agent being combined with an excess of pharmaceutically acceptable carrier(s) or other carrier intended to facilitate its use. The term isolated, when applied to a polypeptide or polynucleotide as described herein, denotes that the polypeptide or polynucleotide is essentially free of cellular components with which it is associated in the natural state. It may, for example, be in a homogeneous state and may be in a dry or aqueous solution.Purity and homogeneity can be determined using known methods, for example, analytical chemistry techniques such as polyacrylamide gel electrophoresis, column chromatography, etc. Petition 870260056387, dated 10 / 06 / 2026, page 82 / 926 74 / 305 Thin-layer chromatography or high-performance liquid chromatography (HPLC) analysis. A protein that is the predominant species present in a preparation is substantially purified. An isolated or purified polypeptide or polynucleotide is substantially free of other cellular material or culture medium when produced by recombinant techniques, or chemical precursors or other chemicals when chemically synthesized. In various embodiments, the purified polypeptides and / or polynucleotides are at least 60%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% (w / w) separated from, purified, or free of proteins and interfering contaminants from production or purification. Often, an agent is the predominant macromolecular species remaining after its purification. HBV polymerase polypeptide variants

[0052] In several embodiments, truncated and / or internally deleted mutant hepatitis B virus (HBV) polymerase polypeptides are provided.

[0053] Wild-type HBV polymerase has four domains, arranged in tandem in a single polypeptide, from the N-terminal to the C-terminal: the Hepatadaviridae-conserved terminal protein (TP) domain (amino acid residues 1 to 177), the spacer region (amino acid residues 178 to 335), TP linkage to the reverse transcriptase (RT) domain (amino acid residues 336 to 678; comprising the conserved NCBI pfam00078 or cd01645 domain), and the C-terminal RNase H (RH) domain (amino acid residues 679 to 832). See, for example, Lanford, et al., J. Virol. (1999) 73(3): 188593; Võrõs, et al., J Virol. (2014) 88(5):2584-99 and Jones, et al., J Virol. (2014) 88(3):1564-72. In the HBV polymerase variants described here, all or part of the spacer region has been eliminated or removed. In the HBV polymerase truncation mutants, the domain Petition 870260056387, dated 10 / 06 / 2026, page 83 / 926 75 / 305 of the entire TP was deleted or removed.

[0054] In general, the enzymatic domains, that is, the reverse transcriptase and RNase H domains, are inactivated in the HBV polymerase protein mutants described herein. In several embodiments, the reverse transcriptase domain does not comprise a YMDD motif (SEQ ID NO: 97). In some embodiments, the YMDD motif (SEQ ID NO: 97) in the reverse transcriptase domain is replaced by YMHD (SEQ ID NO: 99). In some embodiments, the RNase H domain does not comprise an AELL motif (SEQ ID NO: 98). In some embodiments, the AELL motif (SEQ ID NO: 98) in the RNase H domain is replaced by AHLL (SEQ ID NO: 100). truncated polymerase mutants

[0055] In some embodiments, truncated HBV polymerase polypeptides comprise an inactivated reverse transcriptase domain and an inactivated RNase H, wherein the polypeptide does not comprise the entire terminal protein (TP) domain and does not comprise all or part of the spacer domain (i.e., the terminal protein (TP) domain and all or part of the spacer domain is removed, excised, or deleted). In the truncated HBV polymerase polypeptides described herein, the entire TP domain and all or part of the spacer domain or region are deleted or removed. For example, in some embodiments, the 300 N-terminal amino acids of a native or wild-type HBV polymerase are deleted or removed from the truncated HBV polymerase polypeptides described herein. In several embodiments, the inactivated reverse transcriptase domain and the inactivated RNase H can be directly fused or functionally linked or connected via a linker, as described herein.In some embodiments, the truncated HBV polymerase polypeptide is no longer than 600 amino acids in length, for example, it is no longer than 595, 590, 585, 580, 575, 570, 565, 560, 555, 550, 545, 540, or 535 amino acids. Petition 870260056387, dated 10 / 06 / 2026, p. 84 / 926 76 / 305 amino acids in length. In some embodiments, the truncated HBV polymerase polypeptides comprise the C-terminal amino acids 528, 529, 530, 531, 532, 533, 534, or 535 of a polymerase of Native or wild HBV.

[0056] In some embodiments, the truncated HBV polymerase polypeptides comprise an amino acid sequence corresponding to amino acid residues 300 to 832, 301 to 832, 302 to 832, 303 to 832, 304 to 832, 305 to 832, 306 to 832, 307 to 832, 308 to 832, 309 to 832, 310 to 832, 311 to 832, 312 to 832, 313 to 832, 314 to 832, 315 to 832, 316 to 832, 317 to 832, 318 to 832, 319 to 832, 320 a 832, 325 a 832, 326 a 832, 327 a 832, 328 a 832, 329 a832, 330 to 832, 331 to 832, 332 to 832, 333 to 832, 334 to 832, 335 to 832, or 336 to 832 of a native or wild-type HBV polymerase. As used herein, the numbering of a given amino acid polymer or nucleic acid polymer corresponds to, corresponds to, or relates to the numbering of a selected or reference amino acid polymer or nucleic acid polymer when the position of any polymer component (e.g., amino acid, nucleotide, also generically referred to as a residue) is designated by reference to the same position or an equivalent position (e.g., based on an optimal alignment or consensus sequence) in the selected amino acid or nucleic acid polymer, rather than the actual numerical position of the component in the supplied polymer. In several embodiments, the truncated HBV polymerase polypeptides comprise an amino acid sequence corresponding to amino acid residues 300 to 832.In such embodiments, the amino-terminal corresponds to amino acid position 300 of the prototype Pol protein of genotype D. The 6 N-terminal amino acid residues of this sequence are SARSQS (SEQ ID NO: 95) in the Pol antigen of genotype D, and SSRSQS (SEQ ID NO: 96) in the antigen. Petition 870260056387, dated 10 / 06 / 2026, p. 85 / 926 77 / 305 Pol of genotype B. Reports in the literature have indicated that this N-terminal initiation site allows for RT domain function (see, for example, Lanford, et al., above) and truncated protein expression in vitro (see, for example, Võrõs, et al., above).

[0057] In some embodiments, the truncated HBV polymerase polypeptide is of HBV genotype B and comprises or consists of an amino acid sequence from SEQ ID NO: 13, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the truncated HBV polymerase polypeptide is of HBV genotype B and does not comprise a polypeptide sequence (i.e., the sequence is deleted, excised, or removed; the sequence is not included) from SEQ ID NO: 50, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 50.

[0058] In some embodiments, the truncated HBV polymerase polypeptide is of HBV genotype D and comprises or consists of an amino acid sequence of SEQ ID NO: 14, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 14. In some embodiments, the truncated HBV polymerase polypeptide is of HBV genotype D and does not comprise a polypeptide sequence of SEQ ID NO: 51, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 51.

[0059] Modifications can be made to the structure of the polynucleotides that encode such polypeptides, described herein, and still obtain a functional molecule that encodes a variant or derived polypeptide with desirable characteristics (e.g., immunogenic). Petition 870260056387, dated 10 / 06 / 2026, p. 86 / 926 78 / 305 When it is desired to alter the amino acid sequence of a polypeptide to create an equivalent, or even a variant or improved portion of a polypeptide described in this document, the person skilled in the art will typically change one or more of the codons in the coding DNA sequence.

[0060] For example, certain amino acids can be substituted for other amino acids in a protein structure without appreciable loss of its ability to bind other polypeptides (e.g., antigens) or cells. Since it is the binding capacity and nature of a protein that defines the biological functional activity of the protein, certain amino acid sequence substitutions can be made in a protein sequence and, naturally, its underlying DNA coding sequence, and yet obtain a protein with similar properties. It is therefore contemplated that various alterations can be made to the polypeptide sequences of the revealed polypeptides or to the corresponding DNA sequences encoding those polypeptides without appreciable loss of their biological utility or activity.

[0061] A substitution, as used in this document, denotes the replacement of one or more amino acids or nucleotides with different amino acids or nucleotides, respectively.

[0062] In many cases, a polypeptide variant will contain one or more conservative substitutions. A conservative substitution is one in which an amino acid is replaced by another amino acid that has similar properties, so that one versed in the technique of peptide chemistry would expect the secondary structure and hydropathic nature of the polypeptide to remain substantially unchanged.

[0063] As used herein, identity means the percentage of identical nucleotide or amino acid residues at positions Petition 870260056387, dated 10 / 06 / 2026, p. 87 / 926 79 / 305 matches are achieved in two or more sequences when the sequences are aligned to maximize sequence matching, that is, taking into account gaps and insertions. Sequences are generally aligned for maximum matching along a designated region, for example, a region with at least 20, 25, 30, 35, 40, 45, 50, 55, 60, 65 or more amino acids or nucleotides in length, and may be up to the total length of the reference polypeptide or polynucleotide sequence. For sequence comparison, typically one sequence acts as a reference sequence, to which the test sequences are compared. When using a sequence comparison algorithm, the test and reference sequences are entered into a computer program, subsequence coordinates are assigned, if necessary, and the sequence algorithm program parameters are assigned. Otherwise, default parameters may be used.The sequence comparison algorithm then calculates the percentage of sequence identity for the test sequence (or sequences) with respect to the reference sequence, based on the designated program parameters.

[0064] When comparing polynucleotide and polypeptide sequences, two sequences are considered identical if the nucleotide or amino acid sequence in the two sequences is the same when aligned for maximum match, as described below. Comparisons between two sequences are typically performed by comparing the sequences in a comparison window to identify and compare local regions of sequence similarity. A comparison window, for use in the present invention, refers to a segment of at least about 20 contiguous positions, generally 30 to about 75, 40 to about 50, or along the entire length of a sequence, in which one sequence can be compared to another. Petition 870260056387, dated 10 / 06 / 2026, p. 88 / 926 80 / 305 reference of the same number of contiguous positions after the two sequences are optimally aligned.

[0065] Optimal sequence alignment for comparison can be conducted using the Megalign program in the Lasergene bioinformatics software package (DNASTAR, Inc., Madison, WI), using standard parameters. This program incorporates several alignment schemes described in the following references: Dayhoff, MO (1978) A model of evolutionary change in proteins - Matrices for detecting distant relationships. In Dayhoff, MO (ed.) Atlas of Protein Sequence and Structure, National Biomedical Research Foundation, Washington DC, USA, Volume 5, Suppl. 3, pages 345-358; Hein J. (1990) Unified Approach to Alignment and Phylogenes pages 626 to 645, Methods in Enzymology volume 183, Academic Press, Inc., San Diego, CA, USA; Higgins, DG and Sharp, PM (1989) CABIOS 5: 151-153; Myers, E. W. and Muller W. (1988) CABIOS 4:11-17; Robinson, E. D. (1971) Comb. Theor 77: 105; Santou, N. Nes, M. (1987) Mol. Biol. Evolution. 4:406-425; Sneath, PHA and Sokal, RR(1973) Numerical Taxonomy - the Principles and Practice of Numerical Taxonomy, Freeman Press, San Francisco, CA, USA; Wilbur, W.J. and Lipman, DJ (1983) Proc. Natl. Acad., Sci. USA 80:726-730.

[0066] Alternatively, optimal sequence alignment for comparison can be performed using the local identity algorithm of Smith and Waterman (1981) Add. APL. Math 2:482, the identity alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol. 48:443, the search-by-similarity method of Pearson and Lipman (1988) Proc. Natl. Acad. Sci. EUA 85: 2444, computerized implementations of these algorithms (GAP, BESTFIT, BLAST, FASTA and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group (GCG), 575 Science Dr., Madison, WI), or by inspection.

[0067] An example of suitable algorithms for determining the Petition 870260056387, dated 10 / 06 / 2026, pp. 89 / 926 81 / 305 percentage of sequence identity and sequence similarity are determined by the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al. (1977) Nucl. Acids Res. 25:3389-3402 and Altschul et al. (1990) J. Mol. Biol. 215:403-410, respectively. BLAST and BLAST 2.0 can be used, for example, with the parameters described in this document, to determine the percentage of sequence identity for the polynucleotides and polypeptides described in this document. The software for performing BLAST analyses is publicly available from the National Center for Biotechnology Information (blast.ncbi.nlm.nih.gov / Blast.cgi).

[0068] In an illustrative example, cumulative scores can be calculated using, for nucleotide sequences, the parameters M (reward score for a matching residue pair; always > 0) and N (penalty score for non-matching residues; always < 0). The extension of word matches in each direction is interrupted when: the cumulative alignment score falls by an amount X from its maximum value reached; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of each sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a word length (W) of 11, and an expectation (E) of 10, and the alignments of the BLOSUM62 scoring matrix (see Henikoff and Henikoff (1989) Natl. Acad. Sci.USA 89: 10915), (B) of 50, expectation (E) of 10, M = 5, N = -4 and a comparison of both tapes.

[0069] For amino acid sequences, a scoring matrix can be used to calculate the cumulative score. The extension of word hits in each direction is interrupted when: the score Petition 870260056387, dated 10 / 06 / 2026, pp. 90 / 926 82 / 305 of cumulative alignment falls by an amount X from its maximum value reached; the cumulative score goes to zero or below due to the accumulation of one or more negative score residual alignments; or the end of each sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment.

[0070] In one approach, the percentage of sequence identity is determined by comparing two optimally aligned sequences along a comparison window of at least 20 positions, for example, at least 50 positions, at least 100 positions, or along the entire length of a reference sequence, wherein the portion of the polynucleotide or polypeptide sequence in the comparison window may comprise additions or deletions (i.e., gaps) of 20 percent or less, generally 5 to 15 percent, or 10 to 12 percent, compared to the reference sequences (which do not comprise additions or deletions) for optimal alignment of the two sequences.The percentage is calculated by determining the number of positions at which identical nucleic acid bases or amino acid residues occur in both sequences to yield the number of matching positions, dividing the number of matching positions by the total number of positions in the reference sequence (i.e., the window size), and multiplying the results by 100 to yield the percentage of sequence identity.

[0071] A polypeptide variant, as the term is used herein, is a polypeptide that typically differs from a polypeptide specifically disclosed herein in one or more substitutions, deletions, additions, and / or insertions. Such variants may be naturally occurring or may be generated synthetically, for example, by modifying one or more of the polypeptide sequences described above in this document and evaluating one or more biological activities of the variant. Petition 870260056387, dated 10 / 06 / 2026, pp. 91 / 926 83 / 305 polypeptide as described herein and / or using any one of several well-known techniques in the art. The term variant may also refer to any naturally occurring or modified molecule comprising one or more nucleotide or amino acid mutations.

[0072] Illustrative HBV polymerase truncation mutants for use in promoting, inducing, or eliciting an immunogenic response, for example, against an HBV-expressed polymerase antigen, are provided in Table A. Illustrative N-terminal sequence segments deleted or removed from, and therefore not contained in, the HBV polymerase truncation mutants described herein are provided in Table B. Table A - Pol300 Mutants - Motifs containing inactivating mutations are underlined (YMDD mutated to YMHD, AELL mutated to AHLL). SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence 13 B 534 MSSRSQSQGPVLSCWWLQFRNSEPCSEY CLCHIVNLIEDWGPCTEHGEHRIRTPRTPA RVTGGVFLVDKNPHNTTESRLVVDFSQFS RGNTRVSWPKFAVPNLQSLTNLLSSNLSW LSLDVSAAFYHLPLHPAAMPHLLVGSSGLS RYVARLSSNSRIINNQHRTMQNLHDSCSR NLYVSLMLLYKTYGRKLHLYSHPIILGFRKIP MGVGLSPFLLAQFTSAICSVVRRAFPHCLA FSYMHDVVLGAKSVQHLESLYAAVTNFLLS LGIHLNPHKTKRWGYSLNFMGYVIGSWGT LPQEHIVQKIKMCFRKLPVNRPIDWKVCQR IVGLLGFAAPFTQCGYPALMPLYACIQAKQ AFTFSPTYKAFLSKQYLHLYPVARQRPGLC QVFADATPTGWGLAIGHQRMRGAFVSPLP IHTAHLLAACFARSRSGAKLIGTDNSVVLSR Petition 870260056387, dated 10 / 06 / 2026, pp. 92 / 926 84 / 305 Table A - Pol300 Mutants - Motifs containing inactivating mutations are underlined (YMDD mutated to YMHD, AELL mutated to AHLL). SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence KYTSFPWLLGCAANWILRGTSFVYVPSALN PADDPSRGRLGLYRPLLRLLYRPTTGRTSL YADSPSVPSHLPDRVHFASPLHVAWRPP 14 D 534 MSARSQSERPVFPCWWLQFRNSKPCSDY CLSHIVNLLEDWGPCAEHGEHHIRIPRTPA RVTGGVFLVDKNPHNTAESRLVVDFSQFS RGNYRVSWPKFAVPNLQSLTNLLSSNLSW LSLDVSAAFYHLPLHPAAMPHLLVGSSGLS RYVARLSSNSRIFNYQHGTMQNLHDSCSR NLYVSLMLLYQTFGRKLHLYSHPIILGFRKIP MGVGLSPFLLAQFTSAICSVVRRAFPHCLA FSYMHDVVLGAKSVQHLESLFTAVTNFLLS LGIHLNPNKTKRWGYSLHFMGYVIGCYGSL PQDHIIQKIKECFRKLPVNRPIDWKVCQRIV GLLGFAAPFTQCGYPALMPLYACIQSKQAF TFSPTYKAFLCKQYLNLYPVARQRPGLCQ VFADATPTGWGLVMGHQRMRGTFKAPLPI HTAHLLAACFARSRSGANILGTDNSVVLSR KYTSFPWLLGCAANWILRGTSFVYVPSALN PADDPSRGRLGLYRPLLRLPFRPTTGRTSL YADSPSVPSHLPDRVHFASPLHVAWRPP Table B - N-terminal polypeptide sequence removed from truncated mutants Pol300 SEQ ID NO: HBV Genotype Polypeptide sequence 50 B PLSYQHFRKLLLLDDEAGPLEEELPRLADEGL Petition 870260056387, dated 10 / 06 / 2026, pp. 93 / 926 85 / 305 Tabela B - Sequence of polypeptid GPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGI KPYYPEHVVNHYFQTRHYLHTLWKAGILYKR ESTRSASFCGSPYSWEQDLQHGRLVFQTSK RHGDKSFCPQSPGILPRSSVGPCIQNQLRKS RLGPQPAQGQLAGRQQGGSGSIRARVHPSP WGTVGVEPSGSGHIHNCASNSSSCLHQSAV 51 D IKPYYPEHLVNHYFQTRHYLHTLWKAGILYKR ETTHSASFCGSPYSWEQELQHGAESFHQQS SGILSRPPVGSSLQSKHRKSRLGLQSQQGHL ARRQQGRGWSIRAGIHPTARRPFGVEPSGS GHTANLASKSASCLYQSAVRKAAYPVVSTFK KHSSSGHAVELHNLPPN

[0073] In some embodiments, the truncated HBV polymerase polypeptide does not comprise an amino acid sequence or fragment thereof from another HBV protein. In some embodiments, the truncated HBV polymerase polypeptide does not comprise an amino acid sequence or fragment thereof from an HBV protein selected from the group consisting of precore, core, X, and envelope (e.g., surface antigen). Petition 870260056387, dated 10 / 06 / 2026, pp. 94 / 926 86 / 305 (sAg) small, medium or large). Internal polymerase deletion mutants

[0074] Additionally, mutant HBV polymerase internal deletion polypeptides are provided. In various embodiments, the mutant HBV polymerase internal deletion polypeptide comprises, in sequential order from the N-terminal to the C-terminal, a terminal protein (TP) domain, an inactivated reverse transcriptase domain, an inactivated RNase H, wherein the mutant polypeptide does not comprise all or part of a spacer domain (i.e., all or part of the spacer domain or region is deleted or removed). In several embodiments, the HBV polymerase deletion mutant polypeptide is no longer than 800 amino acids in length, for example, it is no longer than 795, 790, 785, 780, 775, 770, 765, 760, 755, 750, 745, 740, 735, 730, 725, 720, 715, 710, or 705 amino acids in length.In some embodiments, the HBV internal polymerase deletion mutant polypeptides comprise, in sequential order from the N-terminal to the C-terminal, a terminal protein (TP) domain and an amino acid sequence corresponding to amino acid residues 300 to 832, 301 to 832, 302 to 832, 303 to 832, 304 to 832, 305 to 832, 306 to 832, 307 to 832. 832, 308 to 832, 309 to 832, 310 to 832, 311 to 832, 312 to 832, 313a 832, 314 to 832, 315 to 832, 316 to 832, 317 to 832, 318 to 832, 319a 832, 320 to 832, 325 to 832, 326 to 832, 327 to 832, 328 to 832, 329a 832, 330 to 832, 331 to 832, 332 to 832, 333 to 832, 334 to 832, 335a 832 or 336 to 832 of a native or wild-type HBV polymerase. In various embodiments, the terminal protein (TP) domain, the inactivated reverse transcriptase domain, and the inactivated RNase H can independently be directly fused or functionally linked or connected via a linker, for example, as described herein, for example, as provided in Ta Petition 870260056387, dated 10 / 06 / 2026, pp. 95 / 926 87 / 305 beautiful J.

[0075] In some embodiments, the HBV internal polymerase deletion mutant polypeptide is of HBV genotype A and comprises or consists of an amino acid sequence of any of the SEQ ID NOs: 5 and 9, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 5 and 9. In some embodiments, the HBV internal polymerase deletion mutant polypeptide is of genotype A and does not comprise a polypeptide of SEQ ID NO: 42 or 46, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 42 or 46.

[0076] In some embodiments, the HBV internal polymerase deletion mutant polypeptide is of HBV genotype B and comprises or consists of an amino acid sequence of any of the SEQ ID NOs: 6 and 10, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 6 and 10. In some embodiments, the HBV internal polymerase deletion mutant polypeptide is of HBV genotype B and does not comprise a polypeptide of SEQ ID NO: 43 or 47, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 43 or 47.

[0077] In some embodiments, the HBV internal deletion mutant polypeptide is of HBV genotype C and comprises or consists of an amino acid sequence of any of the SEQ ID NOs: 8 and 11, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, Petition 870260056387, dated 10 / 06 / 2026, p. 96 / 926 88 / 305 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 8 and 11. In some embodiments, the HBV internal polymerase deletion mutant polypeptide is of genotype C and does not comprise a polypeptide of SEQ ID NO: 44 or 48, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NO: 44 or 48.

[0078] In some embodiments, the HBV internal polymerase deletion mutant polypeptide is of HBV genotype D and comprises or consists of an amino acid sequence of any of the SEQ ID NOs: 9 and 12, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 9 and 12. In some embodiments, the HBV internal polymerase deletion mutant polypeptide is of HBV genotype D and does not comprise a polypeptide of SEQ ID NO: 45 or 49, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 45 or 49.

[0079] In some embodiments, the mutant internal deletion polypeptide of HBV polymerase does not comprise an amino acid sequence or fragment thereof from another HBV protein. In some embodiments, the mutant internal deletion polypeptide of HBV polymerase does not comprise an amino acid sequence or fragment thereof from an HBV protein selected from the group consisting of precore, core, X, and envelope (e.g., small, medium, or large surface antigen (sAg)).

[0080] Illustrative HBV internal polymerase deletion mutants for use in promoting, inducing, or eliciting an immunogenic response, for example, against a polymerase antigen expressed by Petition 870260056387, dated 10 / 06 / 2026, pp. 97 / 926 89 / 305 HBV, are provided in Tables C and E. Illustrative internal amino acid sequence segments deleted or removed from, and therefore not contained in, the HBV polymerase internal deletion mutants described herein, for example, corresponding to all or part of a region of the HBV polymerase spacer, are provided in Tables D and F. Nucleus-polymerase fusion polypeptides

[0081] In several embodiments, the truncated and internally deleted HBV polymerase polypeptide variants described herein are fused to an HBV core polypeptide. The core polypeptide may be positioned at the N-terminal or C-terminal in the HBV polymerase. Fusion polypeptides are additionally provided comprising, in sequential order from the N-terminal to the C-terminal, an HBV core polypeptide and a truncated or internally deleted HBV polymerase mutant polypeptide, as described herein. In some embodiments, the core-Pol fusion polypeptide comprising the HBV polymerase deletion mutant polypeptide described herein comprises, in sequential order from the N-terminal to the C-terminal, an HBV core polypeptide and an internally deleted HBV polymerase mutant polypeptide, as described herein.

[0082] In some embodiments, the core-fusion polypeptide-Pol comprises or consists of an amino acid sequence of any of the SEQ ID NOs: 19 to 26, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 19 to 26.

[0083] In some embodiments, the HBV internal deletion mutant fusion protein does not comprise an amino acid sequence or fragment thereof of a protein Petition 870260056387, dated 10 / 06 / 2026, pp. 98 / 926 90 / 305 of the HBV selected from the group consisting of X, prenucleus and envelope (e.g., small, medium or large surface antigen (sAg).

[0084] Illustrative nucleus-polymerase fusion proteins for use in promoting, inducing or eliciting an immunogenic response, for example, against a nucleus and / or polymerase antigen expressed by HBV, are provided in Table G. Table C - PiΙΔ1 Mutants: Motifs containing inactivating mutations are underlined (YMDD mutated to YMHD, AELL mutated to AHLL). Amino acids in bold + underlined + italicized mark the deletion site (the last amino acid before the deleted region and the first amino acid after the deleted region).SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence 5 A 755 MPLSYQHFRKLLLLDDETEAGPLEEELPRLA DEDLNRRVAEDLNLGNLNVSIPWTHKVGNF TGLYSSTVPIFNPEWQTPSFPKIHLHEDIANR CQQFVGPLTVNEKRRLRLIMPARFYPNSTKY LPLDKGIKPYYPDHVVNHYFQTRHYLHTLWK AGILYKRETTRSASFCGSPYSWEQELHHGR LVIKTSQRHGDEPFCSQPSGILSRSSVG PE F HSFPPSSARSQSQGPVFSCWWLQFRNTQP CSKYCLSHLVNLLEDWGPCDEHGEHHIRIPR TPARVTGGVFLVDKNPHNTAESRLVVDFSQ FSRGITRVSWPKFAVPNLQSLTNLLSSNLSW LSLDVSAAFYHIPLHPAAMPHLLVGSSGLSR YVARLSSNSRIHNNQHGTLQNLHDSCSRQL YVSLMLLYKTYGRKLHLYSHPIILGFRKIPMG VGLSPFLLAQFTSAICSVVRRAFPHCLAFSY MHDVVLGAKSVQHLESLYTAVTNFLLSLGIH LNPNKTKRWGYSLNFMGYVIGSWGTLPQD HIVQKIKHCFRKLPINRPIDWKVCQRIVGLLG FAAPFTQCGYPALMPLYACIQAKQAFTFSPT YKAFLSKQYLNLYPVARQRPGLCQVFADAT PTGWGLAIGHQRMRGTFVAPLPIHTAHLLAA CFARRSRSGAKLIGTDNSVVLSRKYTSFPWLL GCTANWILRGTSFVYVPSALNPADDPSRGR. Petition 870260056387, dated 10 / 06 / 2026, pp. 99 / 926 91 / 305 Table C - PiΙΔ1 Mutants: Motifs containing inactivating mutations are underlined (YMDD mutated to YMHD, AELL mutated to AHLL). Amino acids in bold + underlined + italicized mark the deletion site (the last amino acid before the deleted region and the first amino acid after the deleted region). SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence LGLYRPLLRLPYRPTTGRTSLYAVSPSVPSH LPVRVHFASPLHVAWRPP 6 B 749 MPLSYQHFRKLLLLDDEAGPLEEELPRLADE GLNRRVAEDLNLGNLNVSIPWTHKVGNFTG LYSSTVPVFNPEWQTPSFPHIHLQEDIINRC QQYVGP LTVNEKRRLKLIM PARFYP NLTKYL PLDKGIKPYYPEHVVNHYFQTRHYLHTLWKA GILYKRESTRSASFCGSPYSWEQDLQHGRL VFQTSKRHGDKSFCPQSPGILPR SE LHHFPP SSSRSQSQGPVLSCWWLQFRNSEPCSEYC LCHIVNLIEDWGPCTEHGEHRIRTPRTPARV TGGVFLVDKNPHNTTESRLVVDFSQFSRGN TRVSWPKFAVPNLQSLTNLLSSNLSWLSLDV SAAFYHLPLHPAAMPHLLVGSSGLSRYVARL SSNSRIINNQHRTMQNLHDSCSRNLYVSLML LYKTYGRKLHLYSHPIILGFRKIPMGVGLSPF LLAQFTSAICSVVRRAFPHCLAFS YMHDVVL GAKSVQHLESLYAAVTNFLLSLGIHLNPHKT KRWGYSLNFMGYVIGSWGTLPQEHIVQKIKMCFRKLPVNRPIDWKVCQRIVGLLGFAAPFT QCGYPALMPLYACIQAKQAFTFSPTYKAFLS KQYLHLYPVARQRPGLCQVFADATPTGWGL AIGHQRMRGAFVSPLPIHTAHLLAACFARSR SGAKLIGTDNSVVLSRKYTSFPWLLGCAAN WILRGTSFVYVPSALNPADDPSRGRLGLYR PLLRLLYRPTTGRTSLYADSPSVPSHLPDRV HFASPLHVAWRPP 7 C 753 MPLSYQHFRKLLLLDDEAGPLEEELPRLADE DLNRRVAEDLNLGNLNVSIPWTHKVGNFTG LYSSTVPVFNPEWQTPSFPHIHLQEDIINRC QQYVGP LTVNEKRRLKLIM PARFYP NLTKYL PLDKGIKPYYPEHTVNH Petition 870260056387, dated 10 / 06 / 2026, page 100 / 926 92 / 305 Table C - PiΙΔ1 Mutants: Motifs containing inactivating mutations are underlined (YMDD mutated to YMHD, AELL mutated to AHLL). Amino acids in bold + underlined + italicized mark the deletion site (the last amino acid before the deleted region and the first amino acid after the deleted region).SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence YFKTRHYLHTLWKAGILYKRETTRSASFC GSPYSWEQELQHGRLVFQTSTRHGDES FCSQSSGILSRSPVG PE LHNFPPSSARS QSEGPLLSCWWLQFRNSKPCSDYCLSHI VNLLEDWGPCTEHGEHNIRIPRTPARVT GGVFLVDKNPHNTTESRLVVDFSQFSRG STHVSWPKFAVPNLQSLTNLLSSNLSWL SLDVSAAFYHLPLHPAAMPHLLVGSSGL SRYVARLSSTSRNINYQHGAMQDLHDSC SRNLYVSLLLLYKTFGRKLHLYSHPIILGF RKIPMGVGLSPFLLAQFTSAICSVVRRAF PHCLAFSYMHDVVLGAKSVQHLESLFTA VTNFLLSLGIHLNPNKTKRWGYSLNFMG YVIGSWGTLPQEHIVLKIKQCFRKLPVNR PIDWKVCQRIVGLLGFAAPFTQCGYPAL MPLYACIQAKQAFTFSPTYKAFLCKQYLN LYPVARQRSGLCQVFADATPTGWGLAV GHQRMRGTFVSPLPIHTAHLLAACFARS RSGAKLIGTDNSVVLSRKYTSFPWLLGC AANWILRGTSFVYVPSALNPADDPSRGR LGLYRPLLRLPFRPTTGRTSLYAVSPSVP SHLPVRVHFASPLHVAWRPP. Petition 870260056387, dated 10 / 06 / 2026, page 101 / 926 93 / 305 Table C - PiΙΔ1 Mutants: Motifs containing inactivating mutations are underlined (YMDD mutated to YMHD, AELL mutated to AHLL). Amino acids in bold + underlined + italicized mark the deletion site (the last amino acid before the deleted region and the first amino acid after the deleted region).SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence 8 D 742 MPLSYQHFRRLLLLDDEAGPLEEELPRL ADEGLNRRVAEDLNLGNLNVSIPWTHKV GNFTGLYSSTVPVFNPHWKTPSFPNIHL HQDIIKKCEQFVGPLTVNEKRRLQLIMPA RFYPNVTKYLPLDKGIKPYYPEHLVNHYF QTRHYLHTLWKAGILYKRETTHSASFCG SPYSWEQELQHGAESFHQQSSGILSRP PVG SELHNLPPNSARSQSERPVFPCWW LQFRNSKPCSDYCLSHIVNLLEDWGPCA EHGEHHIRIPRTPARVTGGVFLVDKNPH NTAESRLVVDFSQFSRGNYRVSWPKFA VPNLQSLTNLLSSNLSWLSLDVSAAFYHL PLHPAAMPHLLVGSSGLSRYVARLSSNS RIFNYQHGTMQNLHDSCSRNLYVSLMLL YQTFGRKLHLYSHPIILGFRKIPMGVGLS PFLLAQFTSAICSVVRRAFPHCLAFSYMH DVVLGAKSVQHLESLFTAVTNFLLSLGIH LNPNKTKRWGYSLHFMGYVIGCYGSLP QDHIIQKIKECFRKLPVNRPIDWKVCQRIV GLLGFAAPFTQCGYPALMPLYACIQSKQ AFTFSPTYKAFLCKQYLNLYPVARQRPG LCQVFADATPTGWGLVMGHQRMRGTFK. Petition 870260056387, dated 10 / 06 / 2026, page 102 / 926 94 / 305 Table C - PiΙΔ1 Mutants: Motifs containing inactivating mutations are underlined (YMDD mutated to YMHD, AELL mutated to AHLL). Amino acids in bold + underlined + italicized mark the deletion site (the last amino acid before the deleted region and the first amino acid after the deleted region). SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence APLPIHTAHLLAACFARSRSGANILGTDN SVVLSRKYTSFPWLLGCAANWILRGTSF VYVPSALNPADDPSRGRLGLYRPLLRLP FRPTTGRTSLYADSPSVPSHLPDRVHFA SPLHVAWRPP Table D - Internal spacer polypeptide sequences removed from PoP1 mutants and PoP1 core fusion proteins SEQ ID NO: HBV Genotype Polypeptide sequence 42 A CIRSQFKQSRLGLQPHQGPLATSQSGRSGSIRAR- VHSPTRRCFGVEPSGSGHIGHSASSSSSCLHQSA- VRKAAYSHLSTSKRQSSSGHAV 43 B SVGPCIQNQLRKSRLGPQPAQGQLAGRQQGGSGSI- RARVHPSPWGTVGVEPSGSGHIHNCAS- NSSSCLHQSAVRKAAYSHISTSKGHSSSGHAV 44 C CIRSQLKQSRLGLQPQQGSLARSKSGRSGSIRAR- VHPTTRQSFGVEPSGSGHIDNSASSASSCLHQSA- VRKTAYSHLSTSKRQSSSGHAV 45 D SLQSKHRKSRLGLQSQQGHLARRQQGRGWSIRAGIHPTARRPFGVEPSGSGHTANLASKSASCLYQSAVRKAAYPVVSTFKKHSSSGHAV Petition 870260056387, dated 10 / 06 / 2026, page 103 / 926 95 / 305 Table E - PiΙΔ3 Mutants - Motifs containing inactivating mutations are underlined (YMDD mutated to YMHD, AELL mutated to AHLL). Amino acids in bold + underlined + italicized mark the deletion site (the last amino acid before the deleted region and the first amino acid after the deleted region).SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence 9 A 705 MPLSYQHFRKLLLLDDETEAGPLEEELP RLADEDLNRRVAEDLNLGNLNVSIPWT HKVGNFTGLYSSTVPIFNPEWQTPSFP KIHLHEDIANRCQQFVGPLTVNEKRRLR LIMPARFYPNSTKYLPLDKGIKPYYPDH VVNHYFQTRHYLHTLWKAGILYKRETT RSASFCGSPYSWEQELHH GCWWLQF RNTQPCSKYCLSHLVNLLEDWGPCDE HGEHHIRIPRTPARVTGGVFLVDKNPH NTAESRLVVDFSQFSRGITRVSWPKFA VPNLQSLTNLLSSNLSWLSLDVSAAFY HIPLHPAAMPHLLVGSSGLSRYVARLSS NSRIHNNQHGTLQNLHDSCSRQLYVSL MLLYKTYGRKLHLYSHPIILGFRKIPMGV GLSPFLLAQFTSAICSVVRRAFPHCLAF S YMHD VVLGAKSVQHLESLYTAVTNFL LSLGIHLNPNKTKRWGYSLNFMGYVIG SWGTLPQDHIVQKIKHCFRKLPINRPID WKVCQRIVGLLGFAAPFTQCGYPALMP LYACIQAKQAFTFSPTYKAFLSKQYLNL YPVARQRPGLCQVFADATPTGWGLAIG HQRMRGTFVAPLPIHTAHLLAACFARS RSGAKLIGTDNSVVLSRKYTSFPWLLG CTANWILRGTSFVYVPSALNPADDPSR GRLGLYRPLLRLPYRPTTGRTSLYAVS PSVPSHLPVRVHFASPLHVAWRPP 10 B 703 MPLSYQHFRKLLLLDDEAGPLEEELPRL ADEGLNRRVAEDLNLGNLNVSIPWTHK VGNFTGLYSSTVPVFNPEWQTPSFPHI. Petition 870260056387, dated 10 / 06 / 2026, page 104 / 926 96 / 305 Table E - PiΙΔ3 Mutants - Motifs containing inactivating mutations are underlined (YMDD mutated to YMHD, AELL mutated to AHLL). Amino acids in bold + underlined + italicized mark the deletion site (the last amino acid before the deleted region and the first amino acid after the deleted region).SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence HLQEDIINRCQQYVGPLTVNEKRRLKLI MPARFYPNLTKYLPLDKGIKPYYPEHVV NHYFQTRHYLHTLWKAGILYKRESTRS ASFCGSPYSWEQDLQH GCWWLQFRN SEPCSEYCLCHIVNLIEDWGPCTEHGE HRIRTPRTPARVTGGVFLVDKNPHNTT ESRLVVDFSQFSRGNTRVSWPKFAVP NLQSLTNLLSSNLSWLSLDVSAAFYHLP LHPAAMPHLLVGSSGLSRYVARLSSNS RIINNQHRTMQNLHDSCSRNLYVSLML LYKTYGRKLHLYSHPIILGFRKIPMGVGL SPFLLAQFTSAICSVVRRAFPHCLAFSY MHDVVLGAKSVQHLESLYAAVTNFLLS LGIHLNPHKTKRWGYSLNFMGYVIGSW GTLPQEHIVQKIKMCFRKLPVNRPIDWK VCQRIVGLLGFAAPFTQCGYPALMPLY ACIQAKQAFTFSPTYKAFLSKQYLHLYP VARQRPGLCQVFADATPTGWGLAIGH QRMRGAFVSPLPIHTAHLLAACFARSR SGAKLIGTDNSVVLSRKYTSFPWLLGC AANWILRGTSFVYVPSALNPADDDPSRG RLGLYRPLLRLLYRPTTGRTSLYADSPS VPSHLPDRVHFASPLHVAWRPP. Petition 870260056387, dated 10 / 06 / 2026, page 105 / 926 97 / 305 Table E - PiΙΔ3 Mutants - Motifs containing inactivating mutations are underlined (YMDD mutated to YMHD, AELL mutated to AHLL). Amino acids in bold + underlined + italicized mark the deletion site (the last amino acid before the deleted region and the first amino acid after the deleted region).SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence 11 C 703 MPLSYQHFRKLLLLDDEAGPLEEELPRL ADEDLNRRVAEDLNLGNLNVSIPWTHK VGNFTGLYSSTVPVFNPEWQTPSFPHI HLQEDIINRCQQYVGPLTVNEKRRLKLI MPARFYPNLTKYLPLDKGIKPYYPEHTV NHYFKTRHYLHTLWKAGILYKRETTRSA SFCGSPYSWEQELQH GCWWLQFRNS KPCSDYCLSHIVNLLEDWGPCTEHGEH NIRIPRTPARVTGGVFLVDKNPHNTTES RLVVDFSQFSRGSTHVSWPKFAVPNLQ SLTNLLSSNLSWLSLDVSAAFYHLPLHP AAMPHLLVGSSGLSRYVARLSSTSRNI NYQHGAMQDLHDSCSRNLYVSLLLLYK TFGRKLHLYSHPIILGFRKIPMGVGLSPF LLAQFTSAICSVVRRAFPHCLAFSYMHD VVLGAKSVQHLESLFTAVTNFLLSLGIHL NPNKTKRWGYSLNFMGYVIGSWGTLP QEHIVLKIKQCFRKLPVNRPIDWKVCQR IVGLLGFAAPFTQCGYPALMPLYACIQA KQAFTFSPTYKAFLCKQYLNLYPVARQ RSGLCQVFADATPTGWGLAVGHQRMR GTFVSPLPIHTAHLLAACFARSRSGAKLI GTDNSVVLSRKYTSFPWLLGCAANWIL RGTSFVYVPSALNPADDPSRGRLGLYR PLLRLPFRPTTGRTSLYAVSPSVPSHLP VRVHFASPLHVAWRPP. Petition 870260056387, dated 10 / 06 / 2026, page 106 / 926 98 / 305 Table E - PiΙΔ3 Mutants - Motifs containing inactivating mutations are underlined (YMDD mutated to YMHD, AELL mutated to AHLL). Amino acids in bold + underlined + italicized mark the deletion site (the last amino acid before the deleted region and the first amino acid after the deleted region).SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence 12 D 703 MPLSYQHFRRLLLLDDEAGPLEEELPRL ADEGLNRRVAEDLNLGNLNVSIPWTHK VGNFTGLYSSTVPVFNPHWKTPSFPNI HLHQDIIKKCEQFVGPLTVNEKRRLQLI MPARFYPNVTKYLPLDKGIKPYYPEHLV NHYFQTRHYLHTLWKAGILYKRETTHS ASFCGSPYSWEQELQH GCWWLQFRN SKPCSDYCLSHIVNLLEDWGPCAEHGE HHIRIPRTPARVTGGVFLVDKNPHNTAE SRLVVDFSQFSRGNYRVSWPKFAVPNL QSLTNLLSSNLSWLSLDVSAAFYHLPLH PAAMPHLLVGSSGLSRYVARLSSNSRIF NYQHGTMQNLHDSCSRNLYVSLMLLY QTFGRKLHLYSHPIILGFRKIPMGVGLS PFLLAQFTSAICSVVRRAFPHCLAFSYM HDVVLGAKSVQHLESLFTAVTNFLLSLG IHLNPNKTKRWGYSLHFMGYVIGCYGS LPQDHIIQKIKECFRKLPVNRPIDWKVC QRIVGLLGFAAPFTQCGYPALMPLYACI QSKQAFTFSPTYKAFLCKQYLNLYPVA RQRPGLCQVFADATPTGWGLVMGHQ RMRGTFKAPLPIHTAHLLAACFARSRS GANILGTDNSVVLSRKYTSFPWLLGCA ANWILRGTSFVYVPSALNPADDPSRGR LGLYRPLLRLPFRPTTGRTSLYADSPSV PSHLPDRVHFASPLHVAWRPP. Petition 870260056387, dated 10 / 06 / 2026, page 107 / 926 99 / 305 Table F - Internal spacer polypeptide sequences removed from PiΙΔ3 mutants and PiοΙΔ3 core fusion proteins SEQ ID NO: HBV Genotype Polypeptide Sequence 46 A RLVIKTSQRHGDEPFCSQPSGILSRSSVGPCIRS QFKQSRLGLQPHQGPLATSQSGRSGSIRARVHS PTRRCFGVEPSGSGHIGHSASSSSSCLHQSAVR KAAYSHLSTSKRQSSSGHAVEFHSFPPSSARSQ SQGPVFS 47 B RLVFQTSKRHGDKSFCPQSPGILPRSSVGPCIQN QLRKSRLGPQPAQGQLAGRQQGGSGSIRARVH PSPWGTVGVEPSGSGHIHNCASNSSSCLHQSAV RKAAYSHISTSKGHSSSGHAVELHHFPPSSSRSQ SQGPVLS 48 C RLVFQTSTRHGDESFCSQSSGILSRSPVGPCIRS QLKQSRLGLQPQQGSLARSKSGRSGSIRARVHP TTRQSFGVEPSGSGHIDNSASSASSCLHQSAVR KTAYSHLSTSKRQSSSGHAVELHNFPPSSARSQ SEGPLLS 49 D AESFHQQSSGILSRPPVGSSLQSKHRKSRLGLQS QQGHLARRQQGRGWSIRAGIHPTARRPFGVEPS GSGHTANLASKSASCLYQSAVRKAAYPVVSTFKK HSSSGHAVELHNLPPNSARSQSERPVFP Petition 870260056387, dated 10 / 06 / 2026, page 108 / 926 100 / 305 Table G - Core Fusion Proteins - Pol SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide Sequence Core Fusion Proteins - Polmut - Core sequences are indicated with bold + underline. Motifs containing inactivation mutations in Pol are underlined (YMDD mutated to YMHD, AELL mutated to AHLL).15 TO 1030 MDIDPYKEFGASVELLSFLPSDFFPSVRD LLDTASALYREALESPEHCSPHHTALRQ AILCWGELMTLATWVGNNLEDPASRDL VVNYVNTNMGLKIRQLLWFHISCLTFGRE TVLEYLVSFGVWIRTPPAYRPPNAPILST LPETTVVRRRDRGRSPRRRTPSPRRRRS QSPRRRRSQSRESQCMPLSYQHFRKLLL LDDETEAGPLEEELPRLADEDLNRRVAE DLNLGNLNVSIPWTHKVGNFTGLYSSTVP IFNPEWQTPSFPKIHLHEDIANRCQQFVG PLTVNEKRRLRLCLIMPARFYPNSTKYLPLD KG IKPYYPDHVVN HYFQTRHYLHTLWKA GILYKRETTRSASFCGSPYSWEQELHHG RLVIKTSQRHGDEPFCSQPSGILSRSSVG PCIRSQFKQSRLGLQPHQGPLATSQSGR SGSIRARVHSPTRCFGVEPSGSGHIGH SASSSSSCLHQSAVRKAAYSHLSTSKRQ SSSGHAVEFHSFPPSSARSQSQGPVFSC WWLQFRNTQPCSKYCLSHLVNLLEDWG PCDEHGEHHIRIPRTPARVTGGVFLVDKN PHNTAESRLVVDFSQFSRGITRVSWPKF AVPNLQSLTNLLSSNLSWLSLDVSAAFYH IPLHPAAMPHLLVGSSGLSRYVARLSSNS RIHNNQHGTLQNLHDSCSRQLYVSLMLL. Petition 870260056387, dated 10 / 06 / 2026, page 109 / 926 101 / 305 Table G - Nucleus-Pol Fusion Proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence YKTYGRKLHLYSHPIILGFRKIPMGVGLSP FLLAQFTSAICSVVRRAFPHCLAFSYMHD VVLGAKSVQHLESLYTAVTNFLLSLGIHLN PNKTKRWGYSLNFMGYVIGSWGTLPQD HIVQKIKHCFRKLPINRPIDWKVCQRIVGL LGFAAPFTQCGYPALMPLYACIQAKQAFT FSPTYKAFLSKQYLNLYPVARQRPGLCQ VFADATPTGWGLAIGHQRMRGTFVAPLPI HTAHLLAACFARSRSGAKLIGTDNSVVLS RKYTSFPWLLGCTANWILRGTSFVYVPSA LNPADDPSRGRLGLYRPLLRLPYRPTTG RTSLYAVSPSVPSHLPVRVHFASPLHVA WRPP 16 B 1026 MDIDPYKEFGASVELLSFLPSDFFPSVR DLLDTASALYREALESPEHCSPHHTAL RQAILCWGELMNLATWVGSNLEDPAS RELVVSYVNVNMGLKIRQLLWFHISCLT FGRETVLEYLVSFGVWIRTPPAYRPPNA PILSTLPETTVVRRRGRSPRRRTPSPRR RRSQSPRRRRSQSRESQCM PLSYQHF RKLLLLDDEAGPLEEELPRLADEGLNRR VAEDLNLGNLNVSIPWTHKVGNFTGLYS STVPVFNPEWQTPSFPHIHLQEDIINRCQ QYVGPLTVNEKRRLKLIMPARFYPNLTK YLPLDKGIKPYYPEHVVNHYFQTRHYLH TLWKAGILYKRESTRSASFCGSPYSWE QDLQHGRLVFQTSKRHGDKSFCPQSPG ILPRSSVGPCIQNQLRKSRLGPQPAQGQ LAGRQQGGSGSIRARVHPSPWGTVGVE Petition 870260056387, dated 10 / 06 / 2026, page 110 / 926 102 / 305 Table G - Nucleus-Pol Fusion Proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence PSGSGHIHNCASNSSSCLHQSAVRKAA YSHISTSKGHSSSGHAVELHHFPPSSSR SQSQGPVLSCWWLQFRNSEPCSEYCL CHIVNLIEDWGPCTEHGEHRIRTPRTPA RVTGGVFLVDKNPHNTTESRLVVDFSQF SRGNTRVSWPKFAVPNLQSLTNLLSSNL SWLSLDVSAAFYHLPLHPAAMPHLLVGS SGLSRYVARLSSNSRIINNQHRTMQNLH DSCSRNLYVSLMLLYKTYGRKLHLYSHP IILGFRKIPMGVGLSPFLLAQFTSAICSVV RRAFPHCLAFSYMHDVVLGAKSVQHLE SLYAAVTNFLLSLGIHLNPHKTKRWGYS LNFMGYVIGSWGTLPQEHIVQKIKMCFR KLPVNRPIDWKVCQRIVGLLGFAAPFTQ CGYPALMPLYACIQAKQAFTFSPTYKAF LSKQYLHLYPVARQRPGLCQVFADATPT GWGLAIGHQRMRGAFVSPLPIHTAHLLA ACFARSRSGAKLIGTDNSVVLSRKYTSF PWLLGCAANWILRGTSFVYVPSALNPAD DPSRGRLGLYRPLLRLLYRPTTGRTSLY ADSPSVPSHLPDRVHFASPLHVAWRPP 17 C 1026 MDIDPYKEFGASVELLSFLPSDFFPSVR DLLDTASALYREALESPEHCSPHHTAL RQAILCWGELMNLATWVGSNLEDPAS RELVVSYVNVNMGLKIRQLLWFHISCLT FGRETVLEYLVSFGVWIRTPPAYRPPNA PILSTLPETTVVRRRGRSPRRRTPSPRR RRSQSPRRRRSQSRESQCM PLSYQHF RKLLLLDDEAGPLEEELPRLADEDLNRR Petition 870260056387, dated 10 / 06 / 2026, p. 111 / 926 103 / 305 Table G - Nucleus-Pol Fusion Proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide Sequence VAEDLNLGNLNVSIPWTHKVGNFTGLYS STVPVFNPEWQTPSFPHIHLQEDIINRCQ QYVGPLTVNEKRRLKLIMPARFYPNLTK YLPLDKGIKPYYPEHTVNHYFKTRHYLH TLWKAGILYKRETTRSASFCGSPYSWE QELQHGRLVFQTSTRHGDESFCSQSSG ILSRSPVGPCIRSQLKQSRLGLQPQQGS LARSKSGRSGSIRARVHPTTRQSFGVEP SGSGHIDNSASSASSCLHQSAVRKTAYS HLSTSKRQSSSGHAVELHNFPPSSARS QSEGPLLSCWWLQFRNSKPCSDYCLSH IVNLLEDWGPCTEHGEHNIRIPRTPARVT GGVFLVDKNPHNTTESRLVVDFSQFSR GSTHVSWPKFAVPNLQSLTNLLSSNLS WLSLDVSAAFYHLPLHPAAMPHLLVGSS GLSRYVARLSSTSRNINYQHGAMQDLH DSCSRNLYVSLLLLYKTFGRKLHLYSHPII LGFRKIPMGVGLSPFLLAQFTSAICSVVR RAFPHCLAFSYMHDVVLGAKSVQHLESL FTAVTNFLLSLGIHLNPNKTKRWGYSLN FMGYVIGSWGTLPQEHIVLKIKQCFRKLP VNRPIDWKVCQRIVGLLGFAAPFTQCGY PALMPLYACIQAKQAFTFSPTYKAFLCK QYLNLYPVARQRSGLCQVFADATPTGW GLAVGHQRMRGTFVSPLPIHTAHLLAAC FARSRSGAKLIGTDNSVVLSRKYTSFPW LLGCAANWILRGTSFVYVPSALNPADDP SRGRLGLYRPLLRLPFRPTTGRTSLYAV SPSVPSHLPVRVHFASPLHVAWRPPRR Petition 870260056387, dated 10 / 06 / 2026, p. 112 / 926 104 / 305 Table G - Nucleus-Pol Fusion Proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide Sequence RSQSRESQCMPLSYQHFRKLLLLDDEA GPLEEELPRLADEDLNRRVAEDLNLGNL NVSIPWTHKVGNFTGLYSSTVPVFNPE WQTPSFPHIHLQEDIINRCQQYVGPLTV NEKRRLKLIMPARFYPNLTKYLPLDKGIK PYYPEHTVNHYFKTRHYLHTLWKAGILY KRETTRSASFCGSPYSWEQELQHGRLV FQTSTRHGDESFCSQSSGILSRSPVGPC IRSQLKQSRLGLQPQQGSLARSKSGRS GSIRARVHPTTRQSFGVEPSGSGHIDNS ASSASSCLHQSAVRKTAYSHLSTSKRQS SSGHAVELHNFPPSSARSQSEGPLLSC WWLQFRNSKPCSDYCLSHIVNLLEDWG PCTEHGEHNIRIPRTPARVTGGVFLVDK NPHNTTESRLVVDFSQFSRGSTHVSWP KFAVPNLQSLTNLLSSNLSWLSLDVSAA FYHLPLHPAAMPHLLVGSSGLSRYVARL SSTSRNINYQHGAMQDLHDSCSRNLYV SLLLLYKTFGRKLHLYSHPIILGFRKIPMG VGLSPFLLAQFTSAICSVVRRAFPHCLAF SYMHDVVLGAKSVQHLESLFTAVTNFLL SLGIHLNPNKTKRWGYSLNFMGYVIGS WGTLPQEHIVLKIKQCFRKLPVNRPIDW KVCQRIVGLLGFAAPFTQCGYPALMPLY ACIQAKQAFTFSPTYKAFLCKQYLNLYPV ARQRSGLCQVFADATPTGWGLAVGHQ RMRGTFVSPLPIHTAHLLAACFARSRSG AKLIGTDNSVVLSRKYTSFPWLLGCAAN WILRGTSFVYVPSALNPADDDPSRGRLGL Petition 870260056387, dated 10 / 06 / 2026, page 113 / 926 105 / 305 Table G - Nucleus-Pol Fusion Proteins SEQ ID NO: Genótipo do HBV Comprimento (n° de aminoácidos) Sequência de polipeptídeos YRPLLRLPFRPTTGRTSLYAVSPSVPSH LPVRVHFASPLHVAWRPP 18 D 1015 MDIDPYKEFGASVELLSFLPSDFFPSVR DLLDTASALYREALESPEHCSPHHTAL RQAILCWGELMNLATWVGVNLEDPAS RDLVVSYVNTNMGLKFRQLLWFHISCL TFGRETVLEYLVSFGVWIRTPPAYRPPN APILSTLPETTVVRRRGRSPRRRTPSPR RRRSQSPRRRRSQSRESQCMPLSYQH FRRLLLLDDEAGPLEEELPRLADEGLNR RVAEDLNLGNNLNVSIPWTHKVGNFTGLY SSTVPVFNPHWKTPSFPNIHLHQDIIKKC EQFVGPLTVNEKRRLQLIMPARFYPNVT KYLPLDKGIKPYYPEHLVNHYFQTRHYL HTLWKAGILYKRETTHSASFCGSPYSWE QELQHGAESFHQQSSGILSRPPVGSSL QSKHRKSRLGLQSQQGHLARRQQGRG WSIRAGIHPTARRPFGVEPSGSGHTANL AS KSAS CLYQ SAVRKAAYPVVSTFKKHS SSGHAVELHNLPPNSARSQSERPVFPC WWLQFRNSKPCSDYCLSHIVNLLEDWG PCAEHGEHHIRIPRTPARVTGGVFLVDK NPHNTAESRLVVDFSQFSRGNYRVSWP KFAVPNLQSLTNLLSSNLSWLSLDVSAA FYHLPLHPAAMPHLLVGSSGLSRYVARL SSNSRIFNYQHGTMQNLHDSCSRNLYV SLMLLYQTFGRKLHLYSHPIILGFRKIPM GVGLSPFLLAQFTSAICSVVRRAFPHCL AFSYMHDVVLGAKSVQHLESLFTAVTNF Petition: 870260056387, on 10 / 06 / 2026, page. 114 / 926 106 / 305Table G - Core Fusion Proteins - Pol SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide Sequence LLSLGIHLNPNKTKRWGYSLHFMGYVIG CYGSLPQDHIIQKIKECFRKLPVNRPIDW KVCQRIVGLLGFAAPFTQCGYPALMPLY ACIQSKQAFTFSPTYKAFLCKQYLNLYPV ARQRPGLCQVFADATPTGWGLVMGHQ RMRGTFKAPLPIHTAHLLAACFARSRSG ANILGTDNSVVLSRKYTSFPWLLGCAAN WILRGTSFVYVPSALNPADDPSRGRLGL YRPLLRLPFRPTTGRTSLYADSPSVPSH LPDRVHFASPLHVAWRPP Core Fusion Proteins - PoP1 - Core sequences are indicated with bold + underline. The motifs containing inactivating mutations in Pol are underlined (YMDD mutated to YMHD, AELL mutated to AHLL). The amino acids in bold + italics mark the deletion site (last amino acid before the deleted region and the first amino acid after the deleted region).19 TO 940 MDIDPYKEFGASVELLSFLPSDFFPSVR DLLDTASALYREALESPEHCSPHHTAL RQAILCWGELMTLATWVGNNLEDPASR DLVVNYVNTNMGLKIRQLLWFHISCLTF GRETVLEYLVSFGVWIRTPPAYRPPNAP ILSTLPETTVVRRRDRGRSPRRRTPSPR RRRSQSPRRRRSQSRESQCM PLSYQH FRKLLLLDDETEAGPLEEELPRLADEDLN RRVAEDLNLGNLNVSIPWTHKVGNFTGL YSSTVPIFNPEWQTPSFPKIHLHEDIANR CQQFVGPLTVNEKRRLRLIMPARFYPNS TKYLPLDKGIKPYYPDHVVNHYFQTRHY. Petition 870260056387, dated 10 / 06 / 2026, page 115 / 926 107 / 305 Table G - Nucleus-Pol Fusion Proteins No DWGPCDEHGEHHIRIPRTPARVTGGVFL VDKNPHNTAESRLVVDFSQFSRGITRVS WPKFAVPNLQSLTNLLSSNLSWLSLDVS AAFYHIPLHPAAMPHLLVGSSGLSRYVA RLSSNSRIHNNQHGTLQNLHDSCSRQL YVSLMLLYKTYGRKLHLYSHPIILGFRKIP MGVGLSPFLLAQFTSAICSVVRRAFPHC LAFSYMHDVVLGAKSVQHLESLYTAVTN FLLSLGIHLNPNKTKRWGYSLNFMGYVI GSWGTLPQDHIVQKIKHCFRKLPINRPID WKVCQRIVGLLGFAAPFTQCGYPALMPL YACIQAKQAFTFSPTYKAFLSKQYLNLYP VARQRPGLCQVFADATPTGWGLAIGHQ RMRGTFVAPLPIHTAHLLAACFARSRSG AKLIGTDNSVVLSRKYTSFPWLLGCTAN WILRGTSFVYVPSALNPADDPSRGRLGL YRPLLRLPYRPTTGRTSLYAVSPSVPSH LPVRVHFASPLHVAWRPP 20 B 932 MDIDPYKEFGASVELLSFLPSDFFPSVR DLLDTASALYREALESPEHCSPHHTAL RQAILCWGELMNLATWVGSNLEDPAS RELVVSYVNVNMGLKIRQLLWFHISCLT FGRETVLEYLVSFGVWIRTPPAYRPPNA PILSTLPETTVVRRRGRSPRRRTPSPRR RRSQSPRRRRSQSRESQCM PLSYQHF Petition: 870260056387, on 10 / 06 / 2026, page. 116 / 926 108 / 305 Table G - Nucleus-Pol Fusion Proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide Sequence RKLLLLDDEAGPLEEELPRLADEGLNRR VAEDLNLGNLNVSIPWTHKVGNFTGLYS STVPVFNPEWQTPSFPHIHLQEDIINRCQ QYVGPLTVNEKRRLKLIMPARFYPNLTK YLPLDKGIKPYYPEHVVNHYFQTRHYLH TLWKAGILYKRESTRSASFCGSPYSWE QDLQHGRLVFQTSKRHGDKSFCPQSPG ILPR SEL HHFPPSSSRSQSQGPVLSCW WLQFRNSEPCSEYCLCHIVNLIEDWGPC TEHGEHRIRTPRTPARVTGGVFLVDKNP HNTTESRLVVDFSQFSRGNTRVSWPKF AVPNLQSLTNLLSSNLSWLSLDVSAAFY HLPLHPAAMPHLLVGSSGLSRYVARLSS NSRIINNQHRTMQNLHDSCSRNLYVSLM LLYKTYGRKLHLYSHPIILGFRKIPMGVG LSPFLLAQFTSAICSVVRRAFPHCLAFSY MHDVVLGAKSVQHLESLYAAVTNFLLSL GIHLNPHKTKRWGYSLNFMGYVIGSWG TLPQEHIVQKIKMCFRKLPVNRPIDWKV CQRIVGLLGFAAPFTQCGYPALMPLYAC IQAKQAFTFSPTYKAFLSKQYLHLYPVAR QRPGLCQVFADATPTGWGLAIGHQRMR GAFVSPLPIHTAHLLAACFARSRSGAKLI GTDNSVVLSRKYTSFPWLLGCAANWILR GTSFVYVPSALNPADDPSRGRLGLYRPL LRLLYRPTTGRTSLYADSPSVPSHLPDR VHFASPLHVAWRPP 21 C 936 MDIDPYKEFGASVELLSFLPSDFFPSVR DLLDTASALYREALESPEHCSPHHTAL Petition 870260056387, dated 10 / 06 / 2026, page 117 / 926 109 / 305 Table G - Nucleus-Pol Fusion Proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence RQAILCWGELMNLATWVGSNLEDPAS RELVVSYVNVNMGLKIRQLLWFHISCLT FGRETVLEYLVSFGVWIRTPPAYRPPNA PILSTLPETTVVRRRGRSPRRRTPSPRR RRSQSPRRRRSQSRESQCMPLSYQHF RKLLLLDDEAGPLEEELPRLADEDLNRR VAEDLNLGNLNVSIPWTHKVGNFTGLYS STVPVFNPEWQTPSFPHIHLQEDIINRCQ QYVGPLTVNEKRRLKLIMPARFYPNLTK YLPLDKGIKPYYPEHTVNHYFKTRHYLH TLWKAGILYKRETTRSASFCGSPYSWE QELQHGRLVFQTSTRHGDESFCSQSSG ILSRSPVG PE LHNFPPSSARSQSEGPLL SCWWLQFRNSKPCSDYCLSHIVNLLED WGPCTEHGEHNIRIPRTPARVTGGVFLV DKNPHNTTESRLVVDFSQFSRGSTHVS WPKFAVPNLQSLTNLLSSNLSWLSLDVS AAFYHLPLHPAAMPHLLVGSSGLSRYVA RLSSTSRNINYQHGAMQDLHDSCSRNL YVSLLLLYKTFGRKLHLYSHPIILGFRKIP MGVGLSPFLLAQFTSAICSVVRRAFPHC LAFSYMHDVVLGAKSVQHLESLFTAVTN FLSSLGIHLNPNKTKRWGYSLNFMGYVI GSWGTLPQEHIVLKIKQCFRKLPVNRPID WKVCQRIVGLLGFAAPFTQCGYPALMPL YACIQAKQAFTFSPTYKAFLCKQYLNLYP VARQRSGLCQVFADATPTGWGLAVGH QRMRGTFVSPLPIHTAHLLAACFARSRS GAKLIGTDNSVVLSRKYTSFPWLLGCAA Petition 870260056387, dated 10 / 06 / 2026, page 118 / 926 110 / 305 Table G - Nucleus-Pol Fusion Proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence NWILRGTSFVYVPSALNPADDPSRGRLG LYRPLLRLPFRPTTGRTSLYAVSPSVPS HLPVRVHFASPLHVAWRPP 22 D 925 MDIDPYKEFGASVELLSFLPSDFFPSVR DLLDTASALYREALESPEHCSPHHTAL RQAILCWGELMNLATWVGVNLEDPAS RDLVVSYVNTNMGLKFRQLLWFHISCL TFGRETVLEYLVSFGVWIRTPPAYRPPN APILSTLPETTVVRRRGRSPRRRTPSPR RRRSQSPRRRRSQSRESQCMPLSYQH FRRLLLLDDEAGPLEEELPRLADEGLNR RVAEDLNLGNLNVSIPWTHKVGNFTGLY SSTVPVFNPHWKTPSFPNIHLHQDIIKKC EQFVGPLTVNEKRRLQLIMPARFYPNVT KYLPLDKGIKPYYPEHLVNHYFQTRHYL HTLWKAGILYKRETTHSASFCGSPYSWE QELQHGAESFHQQSSGILSRPPVG SE L HNLPPNSARSQSERPVFPCWWLQFRN SKPCSDYCLSHIVNLLEDWGPCAEHGE HHIRIP RTPARVTGGVF LVDKNPHNTAE SRLVVDFSQFSRGNYRVSWPKFAVPNL QSLTNLLSSNLSWLSLDVSAAFYHLPLH PAAMPHLLVGSSGLSRYVARLSSNSRIF NYQHGTMQNLHDSCSRNLYVSLMLLYQ TFGRKLHLYSHPIILGFRKIPMGVGLSPF LLAQFTSAICSVVRRAFPHCLAFSYMHD VVLGAKSVQHLESLFTAVTNFLLSLGIHL NPNKTKRWGYSLHFMGYVIGCYGSLPQ DHIIQKIKECFRKLPVNRPIDWKVCQRIV Petition 870260056387, dated 10 / 06 / 2026, p. 119 / 926 111 / 305 Table G - Core Fusion Proteins - Pol SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide Sequence GLLGFAAPFTQCGYPALMPLYACIQSKQ AFTFSPTYKAFLCKQYLNLYPVARQRPG LCQVFADATPTGWGLVMGHQRMRGTF KAPLPIHTAHLLAACFARSRSGANILGTD NSVVLSRKYTSFPWLLGCAANWILRGTS FVYVPSALNPADDPSRGRLGLYRPLLRL PFRPTTGRTSLYADSPSVPSHLPDRVHF ASPLHVAWRPP Core Fusion Proteins - PoP3 - Core sequences are indicated with bold + underline. Motifs containing inactivation mutations in Pol are underlined (YMDD mutated to YMHD, AELL mutated to AHLL). Amino acids in bold + underlined + italicized mark the deletion site (the last amino acid before the deleted region and the first amino acid after the deleted region).23 A 890 MDIDPYKEFGASVELLSFLPSDFFPSVR DLLDTASALYREALESPEHCSPHHTAL RQAILCWGELMTLATWVGNNLEDPASR DLVVNYVNTNMGLKIRQLLWFHISCLTF GRETVLEYLVSFGVWIRTPPAYRPPNAP ILSTLPETTVVRRRDRGRSPRRRTPSPR RRRSQSPRRRRSQSRESQCM PLSYQH FRKLLLLDDETEAGPLEEELPRLADEDLN RRVAEDLNLGNLNVSIPWTHKVGNFTGL YSSTVPIFNPEWQTPSFPKIHLHEDIANR CQQFVGPLTVNEKRRLRLIMPARFYPNS TKYLPLDKGIKPYYPDHVVNHYFQTRHY LHTLWKAGILYKRETTRSASFCGSPYSW EQELHH GCWWLQFRNTQPCSKYCLSH. Petition 870260056387, dated 10 / 06 / 2026, pp. 120 / 926 112 / 305 Table G - Nucleus-Pol Fusion Proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence LVNLLEDWGPCDEHGEHHIRIPRTPARV TGGVFLVDKNPHNTAESRLVVDFSQFS RGITRVSWPKFAVPNLQSLTNLLSSNLS WLSLDVSAAFYHIPLHPAAMPHLLVGSS GLSRYVARLSSNSRIHNNQHGTLQNLHD SCSRQLYVSLMLLYKTYGRKLHLYSHPII LGFRKIPMGVGLSPFLLAQFTSAICSVVR RAFPHCLAFSYMHDVVLGAKSVQHLESL YTAVTNFLLSLGIHLNPNKTKRWGYSLN FMGYVIGSWGTLPQDHIVQKIKHCFRKL PINRPIDWKVCQRIVGLLGFAAPFTQCG YPALMPLYACIQAKQAFTFSPTYKAFLSK 24 B 886 MDIDPYKEFGASVELLSFLPSDFFPSVR DLLDTASALYREALESPEHCSPHHTAL RQAILCWGELMNLATWVGSNLEDPAS RELVVSYVNVNMGLKIRQLLWFHISCLT FGRETVLEYLVSFGVWIRTPPAYRPPNA PILSTLPETTVVRRRGRSPRRRTPSPRR RRSQSPRRRRSQSRESQCM PLSYQHF RKLLLLDDEAGPLEEELPRLADEGLNRR VAEDLNLGNLNVSIPWTHKVGNFTGLYS Petition 870260056387, dated 10 / 06 / 2026, pp. 121 / 926 113 / 305 Table G - Nucleus-Pol Fusion Proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence STVPVFNPEWQTPSFPHIHLQEDIINRCQ QYVGPLTVNEKRRLKLIMPARFYPNLTK YLPLDKGIKPYYPEHVVNHYFQTRHYLH TLWKAGILYKRESTRSASFCGSPYSWE QDLQH GC WWLQFRNSEPCSEYCLCHIV NLIEDWGPCTEHGEHRIRTPRTPARVTG GVFLVDKNPHNTTESRLVVDFSQFSRG NTRVSWPKFAVPNLQSLTNLLSSNLSWL SLDVSAAFYHLPLHPAAMPHLLVGSSGL SRYVARLSSNSRIINNQHRTMQNLHDSC SRNLYVSLMLLYKTYGRKLHLYSHPIILG FRKIPMGVGLSPFLLAQFTSAICSVVRRA FPHCLAFSYMHDVVLGAKSVQHLESLYA AVTNFLLSLGIHLNPHKTKRWGYSLNFM GYVIGSWGTLPQEHIVQKIKMCFRKLPV NRPIDWKVCQRIVGLLGFAAPFTQCGYP ALMPLYACIQAKQAFTFSPTYKAFLSKQ YLHLYPVARQRPGLCQVFADATPTGWG LAIGHQRMRGAFVSPLPIHTAHLLAACFA RSRSGAKLIGTDNSVVLSRKYTSFPWLL GCAANWILRGTSFVYVPSALNPADDPSR GRLGLYRPLLRLLYRPTTGRTSLYADSP SVPSHLPDRVHFASPLHVAWRPP 25 C 886 MDIDPYKEFGASVELLSFLPSDFFPSVR DLLDTASALYREALESPEHCSPHHTAL RQAILCWGELMNLATWVGSNLEDPAS RELVVSYVNVNMGLKIRQLLWFHISCLT FGRETVLEYLVSFGVWIRTPPAYRPPNA PILSTLPETTVVRRRGRSPRRRTPSPRR Petition 870260056387, dated 10 / 06 / 2026, p. 122 / 926 114 / 305 Table G - Nucleus-Pol Fusion Proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide Sequence RRSQSPRRRRSQSRESQCMPLSYQHF RKLLLLDDEAGPLEEELPRLADEDLNRR VAEDLNLGNLNVSIPWTHKVGNFTGLYS STVPVFNPEWQTPSFPHIHLQEDIINRCQ QYVGPLTVNEKRRLKLIMPARFYPNLTK YLPLDKGIKPYYPEHTVNHYFKTRHYLH TLWKAGILYKRETTRSASFCGSPYSWE QELQH GC WWLQFRNSKPCSDYCLSHIV NLLEDWGPCTEHGEHNIRIPRTPARVTG GVFLVDKNPHNTTESRLVVDFSQFSRG STHVSWPKFAVPNLQSLTNLLSSNLSWL SLDVSAAFYHLPLHPAAMPHLLVGSSGL SRYVARLSSTSRNINYQHGAMQDLHDS CSRNLYVSLLLLYKTFGRKLHLYSHPIILG FRKIPMGVGLSPFLLAQFTSAICSVVRRA FPHCLAFSYMHDVVLGAKSVQHLESLFT AVTNFLLSLGIHLNPNKTKRWGYSLNFM GYVIGSWGTLPQEHIVLKIKQCFRKLPVN RPIDWKVCQRIVGLLGFAAPFTQCGYPA LMPLYACIQAKQAFTFSPTYKAFLCKQYL NLYPVARQRSGLCQVFADATPTGWGLA VGHQRMRGTFVSPLPIHTAHLLAACFAR SRSGAKLIGTDNSVVLSRKYTSFPWLLG CAANWILRGTSFVYVPSALNPADDDPSRG RLGLYRPLLRLPFRPTTGRTSLYAVSPS VPSHLPVRVHFASPLHVAWRPP 26 D 886 MDIDPYKEFGASVELLSFLPSDFFPSVR DLLDTASALYREALESPEHCSPHHTAL RQAILCWGELMNLATWVGVNLEDPAS Petition 870260056387, dated 10 / 06 / 2026, page 123 / 926 115 / 305 Table G - Nucleus-Pol Fusion Proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence RDLVVSYVNTNMGLKFRQLLWFHISCL TFGRETVLEYLVSFGVWIRTPPAYRPPN APILSTLPETTVVRRRGRSPRRRTPSPR RRRSQSPRRRRSQSRESQCMPLSYQH FRRLLLLDDEAGPLEEELPRLADEGLNR RVAEDLNLGNLNVSIPWTHKVGNFTGLY SSTVPVFNPHWKTPSFPNIHLHQDIIKKC EQFVGPLTVNEKRRLQLIMPARFYPNVT KYLPLDKGIKPYYPEHLVNHYFQTRHYL HTLWKAGILYKRETTHSASFCGSPYSWE QELQH GC WWLQFRNSKPCSDYCLSHIV NLLEDWGPCAEHGEHHIRIPRTPARVTG GVFLVDKNPHNTAESRLVVDFSQFSRG NYRVSWPKFAVPNLQSLTNLLSSNLSWL SLDVSAAFYHLPLHPAAMPHLLVGSSGL SRYVARLSSNSRIFNYQHGTMQNLHDS CSRNLYVSLMLLYQTFGRKLHLYSHPIIL GFRKIPMGVGLSPFLLAQFTSAICSVVRR AFPHCLAFSYMHDVVLGAKSVQHLESLF TAVTNFLLSLGIHLNPNKTKRWGYSLHF MGYVIGCYGSLPQDHIIQKIKECFRKLPV NRPIDWKVCQRIVGLLGFAAPFTQCGYP ALMPLYACIQSKQAFTFSPTYKAFLCKQ YLNLYPVARQRPGLCQVFADATPTGWG LVMGHQRMRGTFKAPLPIHTAHLLAACF ARSRSGANILGTDNSVVLSRKYTSFPWL LGCAANWILRGTSFVYVPSALNPADDPS RGRLGLYRPLLRLPFRPTTGRTSLYADS PSVPSHLPDRVHFASPLHVAWRPP Petition 870260056387, dated 10 / 06 / 2026, pp. 124 / 926 116 / 305 Nucleus-sAg fusion proteins

[0085] Fusion proteins are additionally provided, consisting of an N-terminal portion comprising an HBV core polypeptide, or an immunogenic fragment thereof, and a C-terminal portion comprising an HBV small surface antigen, or an immunogenic fragment thereof. In several embodiments, the HBV core polypeptide or fragment thereof and the HBV small surface antigen (sAg), or fragment thereof, are directly fused or contiguous. In some embodiments, the HBV core polypeptide or fragment thereof and the HBV small surface antigen, or fragment thereof, are connected via a linker. HBV core polypeptide or an immunogenic fragment thereof.

[0086] In several embodiments, the HBV core polypeptide, or immunogenic fragment thereof, of the core-sAg fusion protein, independently, may be of an HBV genotype A, B / C, or D. Illustrative HBV core polypeptide amino acid sequences that may be used in the core-sAg fusion proteins described herein are provided in Table H. Table H - Illustrative HBV core polypeptide sequences SEQ ID NO: HBV Genotype Polypeptide sequence 64 A MDIDPYKEFGASVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMTLATWVGNNLEDPASRDLVVNYVNTNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRDRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC Petition 870260056387, dated 10 / 06 / 2026, p. 125 / 926 117 / 305 Table H - Illustrative HBV core polypeptide sequences SEQ ID NO: HBV Genotype Polypeptide Sequence 65 B / C MDIDPYKEFGASVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC 66 D MDIDPYKEFGASVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGVNLEDPASRDLVVSYVNTNMGLKFRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC

[0087] In some embodiments, the core polypeptide in the sAg core fusion polypeptide comprises or consists of an amino acid sequence from any of the SEQ ID NOs: 64 to 66, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 64 to 66. In some embodiments, the core polypeptide comprises a serine (S) residue at the amino acid position corresponding to position 12, and an asparagine (N) residue at the amino acid position corresponding to position 67, wherein the position numbers are with reference to SEQ ID NO:65 or SEQ ID NO:66. Small surface antigen of HBV or an immunogenic fragment thereof.

[0088] In several forms, the HBV core polypeptide, or Petition 870260056387, dated 10 / 06 / 2026, p. 126 / 926 118 / 305 immunogenic fragment of the same, of the nucleoside-sAg fusion protein, independently, can be of an HBV genotype A, B, C, or D. Illustrative HBV sAg polypeptide amino acid sequences that can be used in the nucleoside-sAg fusion proteins described herein are provided in Table 1, in Example 1 below.

[0089] In some embodiments, the sAg polypeptide in the sAg core fusion polypeptide comprises or consists of an amino acid sequence of any of the SEQ ID NOs: 1 to 4, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 1 to 4, for example, one or more of a serine (S) residue at the amino acid position corresponding to position 53, an isoleucine (I) residue at the amino acid position corresponding to position 68, a threonine (T) residue at the amino acid position corresponding to position 125, a proline (P) residue at the amino acid position corresponding to position 127, a phenylalanine (F) residue at the amino acid position corresponding to position 161, a tyrosine (Y) residue at the amino acid position corresponding to position 200, a serine (S) residue at the amino acid position corresponding to position 210,and a leucine (L) residue at the amino acid position corresponding to position 213.

[0090] With regard to core-sAg fusion proteins, the HBV core polypeptide and the HBV sAg polypeptide may be from the same or different HBV genotypes. In some embodiments, the core-sAg fusion protein comprises, in sequential order from the N-terminal to the C-terminal, an HBV core polypeptide and an HBV small surface antigen (sAg) polypeptide, wherein: • The core polypeptide is of HBV genotype A, and the sAg polypeptide is of HBV genotype A. Petition 870260056387, dated 10 / 06 / 2026, page 127 / 926 119 / 305 • the core polypeptide is of an HBV genotype B or C and the sAg polypeptide is of an HBV genotype B; • The core polypeptide is of an HBV genotype B or C, and the sAg polypeptide is of an HBV genotype C; • The core polypeptide is of HBV genotype D, and the sAg polypeptide is of HBV genotype D. • The core polypeptide is of HBV genotype A, and the sAg polypeptide is of HBV genotype B. • The core polypeptide is of HBV genotype A, and the sAg polypeptide is of HBV genotype C. • The core polypeptide is of HBV genotype A, and the sAg polypeptide is of HBV genotype D. • The core polypeptide is of an HBV genotype B or C, and the sAg polypeptide is of an HBV genotype A; • The core polypeptide is of an HBV genotype B or C, and the sAg polypeptide is of an HBV genotype D; • The core polypeptide is of HBV genotype D, and the sAg polypeptide is of HBV genotype A. • The core polypeptide is of HBV genotype D and the sAg polypeptide is of HBV genotype B; or • The core polypeptide is of HBV genotype D and the sAg polypeptide is of HBV genotype C.

[0091] In some embodiments, the Ag nucleofusion protein comprises, in sequential order from the N-terminal to the C-terminal, an HBV core polypeptide and an HBV small surface antigen (sAg) polypeptide, wherein: • The core polypeptide is of HBV genotype B or C, and the sAg polypeptide is of HBV genotype C; or • The core polypeptide is of HBV genotype D, and the sAg polypeptide is of HBV genotype D. Petition 870260056387, dated 10 / 06 / 2026, pp. 128 / 926 120 / 305

[0092] In some embodiments, the Ag core fusion protein comprises, in sequential order, from the N-terminal to the C-terminal, (i) an HBV core polypeptide comprising or consisting of an amino acid sequence of SEQ ID NO: 65, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 65; and (ii) an HBV small surface antigen (sAg) polypeptide comprising or consisting of an amino acid sequence from SEQ ID NO: 3, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 3.

[0093] In some embodiments, the Ag core fusion protein comprises, in sequential order, from the N-terminal to the C-terminal, (i) an HBV core polypeptide comprising or consisting of an amino acid sequence of SEQ ID NO: 66, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 66; and (ii) an HBV small surface antigen (sAg) polypeptide comprising or consisting of an amino acid sequence from SEQ ID NO: 4, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 4.

[0094] In several embodiments, the nucleoside fusion proteins described herein comprise a small surface antigen isoform of HBV, but do not comprise a medium surface antigen isoform of HBV or a large surface antigen isoform of HBV. Consequently, in some embodiments, the nucleoside fusion proteins described herein do not Petition 870260056387, dated 10 / 06 / 2026, p. 129 / 926 121 / 305 comprise a pre-S1 polypeptide of HBV. In some embodiments, the nucleo-sAg fusion proteins described herein do not comprise a pre-S2 polypeptide of HBV. In some embodiments, the nucleo-sAg fusion proteins described herein do not comprise both a pre-S1 polypeptide of HBV and a pre-S2 polypeptide of HBV.

[0095] An illustrative pre-S2 HBV polypeptide not included in the nucleo-sAg fusion protein described here is provided below: MQWNST[A / T]FHQ[T / A]LQDPRVR[A / G]LYFP[A / G]GGSS[L / S]G[A / T][V / I]NPV[L / P]TT[A / V]S[P / H][L / I]SSIF[S / A]RIGDP[A / V][L / M / P / T]N (SEQ ID NO: 79).

[0096] An illustrative HBV pre-S2 consensus polypeptide of HBV genotype A not included in the nucleo-sAg fusion protein described here is provided below: MQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTN (SEQ ID NO: 80).

[0097] An illustrative HBV pre-S2 consensus polypeptide of HBV genotype B not included in the sAg core fusion protein described here is provided below: MQWNSTTFHQTLQDPRVRALYFPAGGSSSGTVSPAQNTVSAISSILSKTGDPVPN (SEQ ID NO: 81).

[0098] An illustrative HBV pre-S2 consensus polypeptide of HBV genotype C not included in the sAg core fusion protein described here is provided below: MQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPN (SEQ ID NO: 82).

[0099] An illustrative HBV pre-S2 consensus polypeptide of HBV genotype D not included in the nucleo-sAg fusion protein described herein is provided below: MQWNSTTFHQTLQDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIPetição 870260056387, de 10 / 06 / 2026, pág. 130 / 926 122 / 305 FSRIGDPALN (SEQ ID NO: 83).

[00100] In some embodiments, the nucleo-sAg fusion proteins described herein do not comprise a pre-S2 HBV polypeptide comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 79 to 83, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 79 to 83.

[00101] An illustrative HBV pre-S1-pre-S2 polypeptide not included in the core-sAg fusion protein described here is provided below: MGQNLSTSNPLGFFPDHQL[D / A]PAFRANT[A / G / R]NPDWDFNPNK DTWPDANKVGAGAFGLGFTPPHGGLLGWSPQAQGI[I / L]QT[L / V]PA NPPPAS[T / A]NRQ[S / T]GRQPTPLSPPLR[N / A]THPQAMQWNST[A / T ]FHQ[T / A]LQDPRVR[A / G]LYFP[A / G]GGSS[L / S]G[A / T][V / I]NPV[L / P ]TT[A / V]S[P / H][L / I]SSIF[S / A]RIGDP[A / V][L / M / P / T]N (SEQ ID NO: 84).

[00102] An illustrative HBV genotype A consensus pre-S1-pre-S2 polypeptide not included in the sAg core fusion protein described here is provided below: MGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWD FNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTI PPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRV RGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTN (SEQ ID NO: 85).

[00103] An illustrative HBV pre-S1-pre-S2 consensus polypeptide of HBV genotype B not included in the nucleo-sAg fusion protein described here is provided below: MGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFKANSENPDWD LNPHKDNWPDANKVGVGAFGPGFTPPHGGLLGWSPQAQGLLTTVP AAPPPASTNRQSGRQPTPLSPPLRDTHPQAMQWNSTTFHQTLQDP Petition 870260056387, dated 10 / 06 / 2026, page 131 / 926 123 / 305 RVRALYFPAGGSSSGTVSPAQNTVSAISSILSKTGDPVPN (SEQ ID NO: 86).

[00104] An illustrative HBV pre-S1-pre-S2 consensus polypeptide of HBV genotype C not included in the nucleo-sAg fusion protein described here is provided below: MGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWD FNPNKDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVP AAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTTFHQALLDP RVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPN (SEQ ID NO: 87).

[00105] An illustrative HBV pre-S1-pre-S2 consensus polypeptide of HBV genotype D not included in the nucleo-sAg fusion protein described here is provided below: MGQNLSTSNPLGFPDHQLDPAFRANTANPDWDFNPNKDTWPDAN KVGAGAFGLGFTPPHGGLLGWSPQAQGILQTLPANPPPASTNRQSG RQPTPLSPPLRNTHPQAMQWNSTTFHQTLQDPRVRGLYFPAGGSS SGTVNPVPTTASPISSIFSRIGDPALN (SEQ ID NO: 88).

[00106] In some embodiments, the nucleo-sAg fusion proteins described herein do not comprise a pre-S1pre-S2 HBV polypeptide comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 84 to 88, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 84 to 88. Optional polypeptide linker

[00107] As appropriate, the HBV core polypeptide and the HBV sAg polypeptide in the core-sAg fusion protein may be directly contiguous or fused, or may be joined, connected, or linked by one or more peptide linkers. In various embodiments, one or more peptide linkers are Petition 870260056387, dated 10 / 06 / 2026, page 132 / 926 124 / 305 selected from one or more of a polyalanine linker, a polyglycine linker, a cleavable linker, a flexible linker, a rigid linker, and combinations thereof, for example, within a linker or within an entire fusion polypeptide. Illustrative fusion protein linkers that can be used in the present fusion polypeptides to connect the HBV core polypeptide and the HBV sAg polypeptide are described, for example, in Chen, et al., Adv Drug Deliv Rev. (2013) 65(10): 1357-1369. In some embodiments, the polyalanine linker comprises or consists of 2 or 3 contiguous alanine residues, for example, AA, AAA, AAY, or AAX, where X is any amino acid (e.g., A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, Y). In some embodiments, a polyglycine linker is used, for example, GG, GGG, GGS, GSG, or GGGS (SEQ ID NO:63). In some embodiments, the cleavable linker is selected from a cleavable 2A peptide.Illustrative cleavable 2A peptides that can be used to connect the HBV core polypeptide and the HBV sAg polypeptide are described, for example, in Donnelly, et al., J. Gen. Virol (2001), 82, 1027-1041 and Chng, et al., mAbs (2015) 7:2, 403-412. Illustrative cleavable 2A peptides that can be used to link the HBV core polypeptide and the HBV sAg polypeptide include, but are not limited to, 2A cleavage sequences (e.g., foot-and-mouth disease virus (F2A), equine rhinitis virus A (E2A), porcine tescovirus-1 (P2A), and Thosea asigna virus (T2A)), optionally in combination with furin recognition / cleavage sequences (e.g., RAKR (SEQ ID NO: 60), REKR (SEQ ID NO: 61), and RRKR (SEQ ID NO: 62)). In certain embodiments, a furin recognition / cleavage sequence (e.g., RAKR (SEQ ID NO: 60), REKR (SEQ ID NO: 61), and RRKR (SEQ ID NO: 62)) is combined or fused with a cleavable 2A peptide. (for example, foot-and-mouth disease virus.) Petition 870260056387, dated 10 / 06 / 2026, p. 133 / 926 125 / 305 (F2A), equine rhinitis virus A (E2A), porcine tescovirus-1 (P2A) and Thosea asigna virus (T2A)) in a single linker. See, for example, Chng, et al., mAbs (2015) 7:2, 403-412. In some embodiments, the linker comprises a porcine tescovirus-1 (P2A) linker. In various embodiments, the cleavable linker 2A comprises or consists of an amino acid sequence of ATNFSLLKQAGDVEENPGP (SEQ ID NO: 56), APVKQTLNFDLLKLAGDVESNPGP (SEQ ID NO: 57), QCTNYALLKLAGDVESNPGP (SEQ ID NO: 58) or EGRGSLLTCGDVEENPGP (SEQ ID NO: 59), or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or at least 99% identical to ATNFSLLKQAGDVEENPGP (SEQ ID NO: 56), APVKQTLNFDLLKLAGDVESNPGP (SEQ ID NO: 57), QCTNYALLKLAGDVESNPGP (SEQ ID NO: 58) or EGRGSLLTCGDVEENPGP (SEQ ID NO: 59).In several embodiments, the cleavable linker 2A comprises or consists of an amino acid sequence of ATNFSLLKQAGDVEENPGP (SEQ ID NO: 56), or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to ATNFSLLKQAGDVEENPGP (SEQ ID NO: 56). As appropriate, in certain embodiments, a furin recognition / cleavage sequence may be positioned at the N-terminus or C-terminus of a 2A linker. In some embodiments, the cleavable linker comprises or consists of a furin recognition / cleavage site selected from RAKR (SEQ ID NO: 60), REKR (SEQ ID NO: 61), and RRKR (SEQ ID NO: 62). Illustrative ligands that can be used to link or connect the HBV core polypeptide and the HBV sAg polypeptide are provided in Table J. Petition 870260056387, dated 10 / 06 / 2026, p. 134 / 926 126 / 305 TABLE J - Illustrative ligands for connecting HBV core polypeptides and HBV sAg in the Ag nucleofusion protein SEQ ID NO: NAME SEQUENCE polyalanine (2) AA polyalanine (3) AAA polyalanine-Tyr AAY polyalanine-XXX AAX (X = any amino acid) polyglycine (2) GG polyglycine (3) GGG polyglycine / serine (3) GGS polyglycine / serine (3) GSG 63 Gly3Ser GGGS 60 furin recognition site RAKR 61 furin recognition site REKR 62 furin recognition site RRKR 56 P2A ATNFSLLKQAGDVEENPGP 57 F2A APVKQTLNFDLLKLAGDVES- NPGP 58 E2A QCTNYALLKLAGDVESNPGP 59 T2A EGRGSLLTCGDVEENPGP

[00108] In some embodiments, the sAg core fusion protein is no longer than 450 amino acids in length, for example, it is no longer than 445, 440, 435, 430, 425, 420, 415 or 410 amino acids in length.

[00109] In some embodiments, the nucleus fusion protein Petition 870260056387, dated 10 / 06 / 2026, p. 135 / 926 127 / 305 sAg does not comprise an amino acid sequence or fragment thereof of an HBV protein selected from the group consisting of X, pre-nucleus, pre-S1, pre-S2 and polymerase.

[00110] In some embodiments, the Ag nucleosfusion protein comprises or consists of an amino acid sequence of any of the SEQ ID NOs: 38 to 41, for example, SEQ ID NO: 41, or a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 38 to 41, SEQ ID NO: 41. In some embodiments, the fusion polypeptide comprises one or more of a serine (S) residue at the amino acid position corresponding to position 12, an asparagine (N) residue at the amino acid position corresponding to position 67, a valine (V) residue at the amino acid position corresponding to position 74, a phenylalanine (F) residue at the amino acid position corresponding to position 97, a residue of threonine (T) at the amino acid position corresponding to position 249, a threonine (T) residue at the amino acid position corresponding to position 250, a serine (S) residue at the amino acid position corresponding to position 317,a serine (S) residue at the amino acid position corresponding to position 318, an arginine (R) residue at the amino acid position corresponding to position 326, a tyrosine (Y) residue at the amino acid position corresponding to position 338, a glycine (G) residue at the amino acid position corresponding to position 363, and an alanine (A) residue at the amino acid position corresponding to position 372, wherein the position numbers are with reference to SEQ ID NO:41.

[00111] Illustrative nucleoside-sAg fusion proteins, for example, for use in promoting, inducing or eliciting an immunogenic response, for example, against the small core and / or surface antigens expressed by HBV, are provided in Table K. Petition 870260056387, dated 10 / 06 / 2026, page 136 / 926 128 / 305 Table K - sAg core fusion proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence sAg core fusion proteins - Core sequences are indicated with bold + underline. Flexible GSG ligand indicated by italics. Cleavable P2A ligand indicated by underline. 38 Core: B / C sAg: C 409 MDIDPYKEFGASVELLSFLPSDFFPS VRDLLDTASALYREALESPEHCSPH HTALRQAILCWGELMNLATWVGSNL EDPASRELVVSYVNVNMGLKIRQLL WFHISCLTFGRETVLEYLVSFGVWIR TPPAYRPPNAPILSTLPETTVVRRRG RSPRRRRTPSPRRRRSQSPRRRRSQ SRESQCMESTTSGFLGPLLVLQAGF FLLTRILTIPQSLDSWWTSLNFLGGAP TCPGQNSQSPTSNHSPTSCPPICPG YRWMCLRRFIIFLCILLLCLIFLLVLLDY QGMLPVCPLIPGSSTTSTGPCKTCTT PAQGTSMFPSCCCTKPTDGNCTCIPI PSSWAFARFLWEWASVRFSWLSLLV PFVQWFVGLSPTVWLSVIWMMWYW GPSLYNILSPFLPLLPIFFCLWVYI 39 Core: B / C sAg: C 430 MDIDPYKEFGASVELLSFLPSDFFPS VRDLLDTASALYREALESPEHCSPH HTALRQAILCWGELMNLATWVGSNL EDPASRELVVSYVNVNMGLKIRQLL WFHISCLTFGRETVLEYLVSFGVWIR TPPAYRPPNAPILSTLPETTVVRRRG RSPRRRRTPSPRRRRSQSPRRRRSQ Petition 870260056387, dated 10 / 06 / 2026, page 137 / 926 129 / 305 Table K - Nucleus-sAg fusion proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence SRESQC GSG ATNFSLLKQAGDVEEN PGPESTTSGFLGPLLVLQAGFFLLTRI LTIPQSLDSWWTSLNFLGGAPTCPG QNSQSPTSNHSPTSCPPICPGYRWM CLRRFIIFLCILLLCLIFLLVLLDYQGML PVCPLIPGSSTTSTGPCKTCTTPAQG TSMFPSCCCTKPTDGNCTCIPIPSSW AFARFLWEWASVRFSWLSLLVPFVQ WFVGLSPTVWLSVIWMMWYWGPSL YNILSPFLPLLPIFFCLWVYI 40 Nucleus: D sAg: D 409 MDIDPYKEFGASVELLSFLPSDFFPS VRDLLDTASALYREALESPEHCSPH HTALRQAILCWGELMNLATWVGVNL EDPASRDLVVSYVNTNMGLKFRQLL WFHISCLTFGRETVLEYLVSFGVWIR TPPAYRPPNAPILSTLPETTVVRRRG RSPRRRTPSPRRRRSQSPRRRRSQ SRESQCMENITSGFLGPLLVLQAGFF LLTRILTIPQSLDSWWTSLNFLGGTTV CLGQNSQSPTSNHSPTSCPPICPGY RWMCLRRFIIFLFILLLCLIFLLVLLDYQ GMLPVCPLIPGSSTTSTGPCRTCTTP AQGTSMYPSCCCTKPSDGNCTCIPIP SSWAFGKFLWEWASARFSWLSLLVP FVQWFVGLSPTVWLSVIWMMWYWG PSLYSILSPFLPLLPIFFCLWVYI Petition 870260056387, dated 10 / 06 / 2026, page 138 / 926 130 / 305 Table K - Nucleus-sAg fusion proteins SEQ ID NO: HBV Genotype Length (number of amino acids) Polypeptide sequence 41 Core: D sAg: D 430 MDIDPYKEFGASVELLSFLPSDFFPS VRDLLDTASALYREALESPEHCSPH HTALRQAILCWGELMNLATWVGVNL EDPASRDLVVSYVNTNMGLKFRQLL WFHISCLTFGRETVLEYLVSFGVWIR TPPAYRPPNAPILSTLPETTVVRRRG RSPRRRTPSPRRRRSQSPRRRRSQ SRESQC GSGATNFSLLKQ 41 Core: D sAg: D 430 AGDVEENPGPENITSGFLGPLLVLQA GFFLLTRILTIPQSLDSWWTSLNFLGG TTVCLGQNSQSPTSNHSPTSCPPICP GYRWMCLRRFIIFLFILLLCLIFLLVLLD YQGMLPVCPLIPGSSTTSTGPCRTCT TPAQGTSMYPSCCCTKPSDGNCTCI PIPSSSWAFGKFLWEWASARFSWLSL LVPFVQWFVGLSPTVWLSVIWMMW YWGPSLYSILSPFLPLLPIFFCLWVYI Sequences of signals or initiation

[00112] In several embodiments, the immunogenic polypeptides described herein comprise a signal sequence or signaling peptide, for example, to direct intracellular trafficking of the polypeptide to a proteasomal or lysosomal compartment. In several embodiments, the immunogenic polypeptide comprises a signal sequence at the N-terminal and / or C-terminal. In some embodiments, the immunogenic polypeptide comprises a signal peptide or an N-terminal initiation sequence. In several embodiments, the peptide of Petition 870260056387, dated 10 / 06 / 2026, page 139 / 926 131 / 305 signaling or initiation sequence is from a protein of origin selected from among a serum protein, a cytokine, a chemokine, a chaperone protein, an invariant protein, and a protein that directs proteins to the lysosomal compartment. In some embodiments, the signaling peptide or initiation sequence is from a protein of selected origin among colony-stimulating factor 2 (CSF2, GM-CSF), tissue-type plasminogen activator (PLAT, t-PA), CC motif chemokine ligand 7 (CCL7, MCP-3), CXC motif chemokine ligand 10 (CXCL10, IP-10), beta-catenin 1 (CTNNB1), CD74 (p33; DHLAG; HLADG; Ia-GAMA, invariant chain), serum albumin (ALB), polyubiquitin B / C (UBB / UBC), calreticulin (CALR), vesicular stomatitis virus protein G (VSV-G), lysosome-associated membrane protein 1 (LAMP-1), and lysosome-associated membrane protein 2 (LAMP-2).In several embodiments, the signaling peptide or initiation sequence is selected from an amino acid sequence of any of the SEQ ID NOs: 67 to 76, or a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID NOs: 67 to 76. In certain embodiments, the immunogenic polypeptide comprises N-terminal and C-terminal signal sequences of LAMP-1, for example, SEQ ID NOs: 77 and 78, respectively. Illustrative signal sequences that can be used in the present immunogenic polypeptides are provided in Table L. TABLE L - Illustrative signal sequences SEQ ID NO: name of protein of origin SEQUENCE 67 CSF2, GM-CSF MWLQSLLLLGTVACSISV 68 PLAT, t-PA MDAMKRGLCCVLLLCGAVFVSAR 69 CD74 MHRRRSRSCREDQKPV 70 albumin KWVTFISLLFLFSSAYS 71 β-catenin MRKAAVSHWQQQSYLDSGIHSGATTTAPSLS 72 CCL7, MCP-3 MNPSAAVIFCLILLGLSGTQGILDMAQPVGINTS Petition 870260056387, dated 10 / 06 / 2026, p. 140 / 926 132 / 305 TABLE L - Illustrative signal sequences SEQ ID NO: name of protein of origin SEQUENCE TTCCYRFINKKIPKQRLESYRRTTSSHCPREAVI FKTKLDKEICADPTQWVQDFMKHLDKKTQTP CLASS 73 ubiquitin MQIFK GIPPDQQRLIFAGKLEDGRTLSDYNIQKESTL HLVLRLRGG 74 calreticulin MLLSVPLLLGLLGLAVA 75 VSV-G MKCLLYLAFLFIGVNC 76 CXCL10, IP-10 MNQTAILICCLIFLTLSGIQG 77 N-terminal de LAMP-1 MAPRSARRPLLLLLLLLGLMHCASAAMFMVK NGNGTACIMANFSAAFSVNYDTKSGPKNMTLD LPSDATVVLNRSSCGKENTSDPSLVIAFGRGH TLTLNFTRNATRYSVQLMSFVYNLSDTHLFPNA SSKEIKTVESITDIDKKYRCVSGTQVHMHCAAMTQTQTQTQTQTQTHRFPNA SPTTAPPAPPSPSPSPVPKSPSVDKYNVSGTN GTCLLASMGLQLNLTYERKDNTTVTRLLNINPN KTSASGSCGAHLVTLELHSEGTTVLLFQFGMN ASSSRFFLQGIQLNTlLPDARDPAFKAANGSLR ALQATVGNSYKCNAEHVRVTKAFSVKVNIV VQAFKVEGGQFGSVEECLLDENSLEDI 78 C-terminal of LAMP-1 GSEFTLIPIAVGGALAGLVIVLIAYLVGRKRSHA GYQTI

[00113] In addition, methods are provided for producing the immunogenic polypeptides described herein. In some implementations, the methods comprise constructing the immunogenic polypeptides using peptide synthesis. In some implementations, the methods comprise constructing, using synthetic or recombinant DNA technology, polynucleotides that encode each Petition 870260056387, dated 10 / 06 / 2026, page 141 / 926 133 / 305 one of the polypeptides of the bivalent antigen and expressing the polypeptides from an expression vector. In some implementations, the methods may further comprise inserting the polynucleotides into one or more vectors and expressing the encoded polypeptides in a cell. This can be done using known recombinant techniques. 3. Polynucleotides that encode immunogenic polypeptides

[00114] Polynucleotides encoding the immunogenic polypeptides described herein are provided, vectors comprising such polynucleotides, and host cells (e.g., human cells, mammalian cells, yeast cells, plant cells, insect cells, bacterial cells, e.g., E. coli) comprising such polynucleotides or expression vectors. Polynucleotides comprising nucleotide sequence(s) encoding any of the immunogenic polypeptides provided herein are provided herein, as well as expression cassettes and vector(s) comprising such polynucleotide sequences, e.g., expression vectors for their efficient expression in host cells, e.g., mammalian cells. In various embodiments, the polynucleotide is a DNA, a cDNA, an mRNA, a self-amplifying RNA (SAM), a self-replicating RNA, or a self-amplifying replicon RNA (RepRNA).In some embodiments, the polynucleotide comprises or is expressed from a self-replicating alphavirus RNA or self-amplifying replicon RNA (RepRNA). Self-replicating RNA and self-amplifying replicon RNA are described as vaccine delivery modes, for example, by Tews, et al., Methods Mol Biol. (2017) 1499:15-35; Démoulins, et al., Methods Mol Biol. (2017) 1499:3775; Englezou, et al., Mol Ther Nucleic Acids. (2018) 12:118-134; McCollough, et al., Vaccines (Basel). (2014) 2(4):735-54; and McCollough, et al., Mol Ther Nucleic Acids. (2014) 3: e173. Petition 870260056387, dated 10 / 06 / 2026, p. 142 / 926 134 / 305

[00115] The terms polynucleotide and nucleic acid molecule refer interchangeably to a polymeric form of nucleotides and includes sense and antisense strands of RNA, cDNA, genomic DNA, and synthetic and mixed polymer forms of the above. As used herein, the term nucleic acid molecule may be interchangeable with the term polynucleotide. In some embodiments, a nucleotide refers to a ribonucleotide, deoxynucleotide, or a modified form of any type of nucleotide and combinations thereof. The terms also include, but are not limited to, single-stranded and double-stranded forms of DNA. In addition, a polynucleotide, for example, a cDNA or mRNA, may include either both naturally occurring and modified nucleotides linked together by naturally occurring and / or unnaturally occurring nucleotide bonds.Nucleic acid molecules may be chemically or biochemically modified, or may contain unnatural or derivatized nucleotide bases, as will be readily appreciated by those skilled in the art. Such modifications include, for example, markers, methylation, substitution of one or more of the naturally occurring nucleotides with an analog, internucleotide modifications such as uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoramidates, carbamates, etc.), charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.), pendant moieties (e.g., polypeptides), intercalators (e.g., acridine, psoralen, etc.), chelating agents, alkylating agents, and modified linkages (e.g., anomeric alpha nucleic acids, etc.). The term above is also intended to include any topological conformation, including single-strand, double-strand, partially duplexed, triple, hairpin, circular, and padlock conformations.A reference to a nucleic acid sequence includes its complement, unless otherwise specified. Thus, a... Petition 870260056387, dated 10 / 06 / 2026, p. 143 / 926 135 / 305 reference to a nucleic acid molecule having a particular sequence should be understood as encompassing its complementary strand, with its complementary sequence. The term also includes polynucleotides with codon usage bias for enhanced expression in a desired viral expression vector or host cell.

[00116] A substitution, as used herein, denotes the replacement of one or more amino acids or nucleotides with different amino acids or nucleotides, respectively.

[00117] An isolated nucleic acid refers to a nucleic acid molecule that has been separated from a component of its natural environment. An isolated nucleic acid includes a nucleic acid molecule contained in cells that normally contain the nucleic acid molecule, but the nucleic acid molecule is present extrachromosomally or in a chromosomal location that is different from its natural chromosomal location.Isolated nucleic acid encoding an immunogenic polypeptide refers to one or more nucleic acid molecules encoding such immunogenic polypeptides, including such nucleic acid molecule(s) in a single vector or multiple separate vectors, and such nucleic acid molecule(s) present in one or more locations on a host cell.

[00118] A polynucleotide variant, as used herein, is a polynucleotide that typically differs from a polynucleotide specifically disclosed herein in one or more substitutions, deletions, additions, and / or insertions. Such variants may be naturally occurring or may be generated synthetically, for example, by modifying one or more of the polynucleotide sequences described herein and evaluating one or more biological activities of the encoded polypeptide as described herein and / or using any of several techniques well known in the art. Petition 870260056387, dated 10 / 06 / 2026, p. 144 / 926 136 / 305

[00119] In some embodiments, the nucleic acid molecule is codon-biased to increase expression in a desired host cell, for example, in human cells, mammalian cells, yeast cells, plant cells, insect cells, or bacterial cells, for example, E. coli cells. Consequently, polynucleotides encoding an immunogenic polypeptide, described herein, are provided, wherein the polynucleotides have codon-use bias, comprise heterologous signal sequences of substitution, and / or have mRNA instability elements eliminated. Methods for generating codon-use biased nucleic acids can be carried out by adapting the methods described, for example, in US patents Nos. 5,965,726; 6,174,666; 6,291,664; 6,414,132; and 6,794,498. Preferred codon usage for the expression of immunogenic polypeptides from viral expression vectors and / or in the desired host cells is provided, for example, at kazusa.org.jp / codon / ; and genscript.com / tools / codon-frequency-table.

[00120] In some embodiments, the polynucleotide encoding an immunogenic polypeptide, as described herein, has 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%, at least 99% identity, or 100% identity with a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 27 to 37 and 89 to 94, as provided in Table M.

[00121] As appropriate, in certain embodiments, the 3' end of a polynucleotide encoding one or more of the immunogenic polypeptides described herein comprises one or multiple tandem stop codons, for example, two or more TAG (amber), TAA (ochre), or TGA (opal or umber) tandem stop codons. The multiple tandem stop codons may be Petition 870260056387, dated 10 / 06 / 2026, p. 145 / 926 137 / 305 equal or different.

[00122] Expression cassettes comprising a polynucleotide encoding an immunogenic polypeptide, as described herein, functionally linked to one or more regulatory sequences are additionally provided. In some embodiments, the polynucleotide is functionally linked to, and under the control of, a constitutive promoter. In some embodiments, the promoter is selected from cytomegalovirus (CMV) primary immediate early, chicken beta-actin (CAG) promoter-fused CMV enhancer, human elongation factor 1α (HEF-1α), mouse cytomegalovirus (mouse CMV), Chinese hamster elongation factor 1α (CHEF-1α), and phosphoglycerate kinase (PGK). Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence 27 B ΡοΙδ1 ATGCCCCTGAGCTACCAGCACTTCAGGAAGC TGCTGCTGCTGGATGGACTGGTCGTCGGG TGGAGGAGGAGCTGCCCAGGCTGGCAGATG AGGGCCTCAACAGGAGAGTGGCAGAGGACC TGAACCTGGGCAACCTGAATGTGAGCATCCCC CTGGACCCACAAAGTGGGGAACTTCACTGG CCTCTACAGCAGCAGTGCCAGTGTTCACCCACCCAC ATCCACCTCCAGGAGGACATCATCAACAGAT GTCAGCAGTATGTGGGCCCTCTGACAGTCAA TGAGAAGAGGAGGCTGAAGCTGATCATGCC TGCCAGGTTCCCCCAACCTGACCAAGTAC CTCCCACTGGACAAGGGCATCAAGCCATACT ATCCTGAGCATGTGGTGAACCACTCACTCAA GACCAGGCACTACCTGCACACACTGTGGAA GGCTGGCATCCTGTACAAGAGGGAGAGCAC CAGATCAGCCTCI II CTGTGGCTCCCCCTAC Petition 870260056387, of 10 / 06 / 2026, p. 146 / 926 138 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence AGCTGGGAGCAGGATCTCCAGCATGGCAGA CTGGTGTTCCAGACCTCCAAGAGGCATGGG GACAAGTCCCCAG Illi GGCCCAG TCCTGCCCAGGAGCGAGCTCCACCACTTCC CCCCCTCCTCCAGCAGAAGCCAGTCCCAGG GACCTGTGCTGTCCTGCTGGTGGCTCCAGTT CAGGAACAGTGAGCCCTGCAGTGAGTACTG TCTGTGTCACATTGTGAACCTGATTGAGGAC TGGGGGCCCT AGGATCAGAACCCCCAGGACCCCAGCCAGA GTGACTGGAGGTGTGTTCCTGGTGGACAAG AACCCCCACAACACCAGAGAGCAGACTG GTGGTGGACTTCTCCCAGIIII CAAGGGGCA ACACCAGAGTGTCCTGGCCCAAGT TT GCAGT GCCCAACCCCAGACCCAGACCGCTGCTG GTCATCAAACCTGAGCTGGCTGTCCCTGGAT GTGTCTGCTGCCTTCTACCACCTGCCCCTGC ACCCTGCAGCCATGCCTCACCTCCTGGTGG GCAGCTCAGGCCTGAGCAGGTATGTGGCCA GGCTGTCAAGCAACTCCAGAATCATCAACAA CCAGCACAGGACCATGCAGAACCTGACCATGCAT CTCTTGCAGCAGGAACCTGTATGTGAGCCTG ATGCTGCTGTACAAGACCTATGGCAGGAAGC TGCACCTGTACTCCCACCCCATCATCCTGGG TTT CAGGAAGATCCCCATGGGAGTGGGACT GTCCCCCTTCCTGCTGGCCCAGTTCACCTCT GCCATCTGCTGAGCTGAGTGAGGGGCTCCCCACTGCCTGGCCTTCTCCTACATGCATG ATGTGGTGCTGGGGGCCAAGTCAGTGCAGC ACCTGGAGTCTCTGTATGCTGCAGTCACCAA Petition 870260056387, dated 10 / 06 / 2026, page 147 / 926 139 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence CTTCCTGCTCAGCCTGGGCATCCACCTGAAC CCCCACAAGACCAAGGTGGGGCTACTCT GGGGCACCCTGCCACAGGAGCACATAGTGC AGAAGATCAAGATGTGCTTCAGGAAGCTGCC AGTGAACAGGCCCATTGATTGGAAGGTGTGC CAGAGGATTGTGGGCCTGCTGGGCT 1 1GCA GCACCCTTCACAGTGTGGCTACCCAGCTC GCAGGCCTTCACCTTCTCCCCCCACTTACAAG GCCTTCCTGTCCCAAGCAGTACCTGCACCTGT ACCCTGTGGCAAGGCAGAGGCCAGGCCTCT GCCAGGTGT TT GCAGATGCCACCCCCACAG GCTGGGGCCTGGCCATTGGCCACCAGAGGA TGAGAGGGGCC TCATT GGACCGCC TCCACACAGCCCACCTGCTGGCAGCATGCTT TGCCAGGTCCAGGTCTGGTGCAAAGCTGATT GGCACTGACAACAGGTGGTGCTGTCCAGA AAGTACACCAGCTTCCCCTGGCTGCTGGGAT GTGCTGCCAACTGGATTCTGAGGGGCACCA GCTTT TGCAGATGACCCCTCCAGGGGCAGACTGGG GCTGTACAGGCCACTGCTCAGACTGCTGTAC AGGCCCACCACTGGCAGAACCTCCCTGTAT GCAGACAGCCCCTCAGTGCCCTCTCACCTG CCAGACAGAGTGCACT TT GCCAGCCCCCTG CATGTTGCCTGGAGGCCCC28ΡΔΔΔATGCCCCTGAGCTACCAGCACTTCAGGAAGC TGCTGCTGCTGGATGATGAGGCTGGCCTCTCTGGAGGAGGAGCTGCCCAGGCTGGCAGATG Petition 870260056387, dated 10 / 06 / 2026, page 148 / 926 140 / 305 Tabela M - Polinucleotídeos que codificam polipeptídeos imunogênicos SEQ ID NO: Genótipo do HBV Nome Sequência de polinucleotídeos AGGGCCTCAACAGGAGAGTGGCAGAGGACC TGAACCTGGGCAACCTGAATGTGAGCATCCC CTGGACCCACAAAGTGGGGAACTTCACTGG CCTCTACAGCAGCACAGTGCCAGTGTTCAAC CCTGAGTGGCAGACCCCCTCCTTCCCCCAC ATCCACCTCCAGGAGGACATCATCAACAGAT GTCAGCAGTATGTGGGCCCTCTGACAGTCAA TGAGAAGAGGAGGCTGAAGCTGATCATGCC TGCCAGGTTCTACCCCAACCTGACCAAGTAC CTCCCACTGGACAAGGGCATCAAGCCATACT ATCCTGAGCATGTGGTGAACCACTACIIICA GACCAGGCACTACCTGCACACACTGTGGAA GGCTGGCATCCTGTACAAGAGGGAGAGCAC CAGATCAGCCTCT i i CTGTGGCTCCCCCTAC AGCTGGGAGCAGGATCTCCAGCATGGCTGC TGGTGGCTCCAGTTCAGGAACAGTGAGCCC TGCAGTGAGTACTGTCTGTGTCACATTGTGA ACCTGATTGAGGACTGGGGGCCCTGCACTG AGCATGGAGAGCACAGGATCAGAACCCCCA GGACCCCAGCCAGAGTGACTGGAGGTGTGT TCCTGGTGGACAAGAACCCCCACAACACCAC AGAGAGCAGACTGGTGGTGGACTTCTCCCA GHH CAAGGGGCAACACCAGAGTGTCCTGG CCCAAGT T T GCAGTGCCCAACCTCCAGAGCC TGACCAACCTGCTGTCATCAAACCTGAGCTG GCTGTCCCTGGATGTGTCTGCTGCCTTCTAC CACCTGCCCCTGCACCCTGCAGCCATGCCTCACCTCCTGGTGGGCAGCTCAGGCCTGAGC AGGTATGTGGCCAGGCTGTCAAGCAACTCCA GAATCATCAACAACCAGCACAGGACCATGCA Petition 870260056387, dated 10 / 06 / 2026, page 149 / 926 141 / 305 Tabela M - Polinucleotídeos que codificam polipeptídeos imunogênicos SEQ ID NO: Genótipo do HBV Nome Sequência de polinucleotídeos GAACCTGCATGACTCTTGCAGCAGGAACCTG TATGTGAGCCTGATGCTGCTGTACAAGACCT ATGGCAGGAAGCTGCACCTGTACTCCCACC CCATCATCCTGGGT 1 1 CAGGAAGATCCCCAT GGGAGTGGGACTGTCCCCCTTCCTGCTGGC CCAGTTCACCTCTGCCATCTGCTCTGTGGTG AGGAGAGCCTTCCCCCACTGCCTGGCCTTCT CCTACATGCATGATGTGGTGCTGGGGGCCA AGTCAGTGCAGCACCTGGAGTCTCTGTATGC TGCAGTCACCAACTTCCTGCTCAGCCTGGGC ATCCACCTGAACCCCCACAAGACCAAGAGGT GGGGCTACTCTCTGAACTTCATGGGCTATGT GATAGGCAGCTGGGGCACCCTGCCACAGGA GCACATAGTGCAGAAGATCAAGATGTGCTTC AGGAAGCTGCCAGTGAACAGGCCCATTGATT GGAAGGTGTGCCAGAGGATTGTGGGCCTGC TGGGCT T T GCAGCACCCTTCACACAGTGTGG CTACCCAGCTCTGATGCCCCTGTATGCCTGC ATCCAGGCCAAGCAGGCCTTCACCTTCTCCC CCACTTACAAGGCCTTCCTGTCCAAGCAGTA CCTGCACCTGTACCCTGTGGCAAGGCAGAG GCCAGGCCTCTGCCAGGTGT T T GCAGATGC CACCCCCACAGGCTGGGGCCTGGCCATTGG CCACCAGAGGATGAGAGGGGCC T T T GTGAG CCCACTGCCAATCCACACAGCCCACCTGCTG GCAGCATGCT T T GCCAGGTCCAGGTCTGGT GCAAAGCTGATTGGCACTGACAACAGTGTGGTGCTGTCCAGAAAGTACACCAGCTTCCCCTG GCTGCTGGGATGTGCTGCCAACTGGATTCTG AGGGGCACCAGCT TT GTCTATGTGCCCTCTG Petition 870260056387, of 10 / 06 / 2026, p. 150 / 926 142 / 305 Tabela M - Polinucleotídeos que codificam polipeptídeos imunogênicos SEQ ID NO: Genótipo do HBV Nome Sequência de polinucleotídeos CACTGAACCCTGCAGATGACCCCTCCAGGG GCAGACTGGGGCTGTACAGGCCACTGCTCA GACTGCTGTACAGGCCCACCACTGGCAGAA CCTCCCTGTATGCAGACAGCCCCTCAGTGCC CTCTCACCTGCCAGACAGAGTGCACI1 1 GCC AGCCCCCTGCATGTTGCCTGGAGGCCCCCC 29 B Pol300 ATGTCCAGCAGAAGCCAGTCCCAGGGACCT GTGCTGTCCTGCTGGTGGCTCCAGTTCAGG AACAGTGAGCCCTGCAGTGAGTACTGTCTGT GTCACATTGTGAACCTGATTGAGGACTGGGG GCCCTGCACTGAGCATGGAGAGCACAGGAT CAGAACCCCCAGGACCCCAGCCAGAGTGAC TGGAGGTGTGTTCCTGGTGGACAAGAACCC CCACAACACCACAGAGAGCAGACTGGTGGT GGACTTCTCCCAGHH CAAGGGGCAACACC AGAGTGTCCTGGCCCAAGT T T GCAGTGCCCA ACCTCCAGAGCCTGACCAACCTGCTGTCATC AAACCTGAGCTGGCTGTCCCTGGATGTGTCT GCTGCCTTCTACCACCTGCCCCTGCACCCTG CAGCCATGCCTCACCTCCTGGTGGGCAGCT CAGGCCTGAGCAGGTATGTGGCCAGGCTGT CAAGCAACTCCAGAATCATCAACAACCAGCA CAGGACCATGCAGAACCTGCATGACTCTTGC AGCAGGAACCTGTATGTGAGCCTGATGCTGC TGTACAAGACCTATGGCAGGAAGCTGCACCT GTACTCCCACCCCATCATCCTGGGT T T CAGG AAGATCCCCATGGGAGTGGGACTGTCCCCCTTCCTGCTGGCCCAGTTCACCTCTGCCATCT GCTCTGTGGTGAGGAGAGCCTTCCCCCACT GCCTGGCCTTCTCCTACATGCATGATGTGGT Petition 870260056387, dated 10 / 06 / 2026, page 151 / 926 143 / 305 Tabela M - Polinucleotídeos que codificam polipeptídeos imunogênicos SEQ ID NO: Genótipo do HBV Nome Sequência de polinucleotídeos GCTGGGGGCCAAGTCAGTGCAGCACCTGGA GTCTCTGTATGCTGCAGTCACCAACTTCCTG CTCAGCCTGGGCATCCACCTGAACCCCCAC AAGACCAAGAGGTGGGGCTACTCTCTGAACT TCATGGGCTATGTGATAGGCAGCTGGGGCA CCCTGCCACAGGAGCACATAGTGCAGAAGA TCAAGATGTGCTTCAGGAAGCTGCCAGTGAA CAGGCCCATTGATTGGAAGGTGTGCCAGAG GATTGTGGGCCTGCTGGGCT 1 1 GCAGCACC CTTCACACAGTGTGGCTACCCAGCTCTGATG CCCCTGTATGCCTGCATCCAGGCCAAGCAG GCCTTCACCTTCTCCCCCACTTACAAGGCCT TCCTGTCCAAGCAGTACCTGCACCTGTACCC TGTGGCAAGGCAGAGGCCAGGCCTCTGCCA GGTGT T T GCAGATGCCACCCCCACAGGCTG GGGCCTGGCCATTGGCCACCAGAGGATGAG AGGGGCC T T T GTGAGCCCACTGCCAATCCA CACAGCCCACCTGCTGGCAGCATGCTTTGC CAGGTCCAGGTCTGGTGCAAAGCTGATTGG CACTGACAACAGTGTGGTGCTGTCCAGAAAG TACACCAGCTTCCCCTGGCTGCTGGGATGTG CTGCCAACTGGATTCTGAGGGGCACCAGCTT TGTCTATGTGCCCTCTGCACTGAACCCTGCA GATGACCCCTCCAGGGGCAGACTGGGGCTG TACAGGCCACTGCTCAGACTGCTGTACAGGC CCACCACTGGCAGAACCTCCCTGTATGCAGA CAGCCCCTCAGTGCCCTCTCACCTGCCAGACAGAGTGCACT TT GCCAGCCCCCTGCATGTT GCCTGGAGGCCCCCC 89 B Pol300 ATGTCTTCAAGATCCCAGAGTCAGGGCCCTG Petition 870260056387, of 10 / 06 / 2026, p. 152 / 926 144 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Sequence of Polynucleotides ori TACT 1 1 CCTGCTGGTGGCTCCAGTTCAGGAA CAGTGAGCCCTGCTCCGAATACTGTCTCTGC CATATCGCTGACTGGACT CCTGTACCGAACATGGAGAACATCGCATCAG GACTCCTAGGACCCCTGCTCGTGTTACAGGC GGGG H m CTTGTTGACAAAAATCCTCACAA TACCACAGAGTCTAGACTCGTGGTGGACTTC TCTCAAMM CTAGGGGGAACACCCGTGTGT CTTGGCAA GTCACTCACCAACCTGTTGTCCTCCAA TTTGT CCTGGTTATCGCTGGATGTGTCTGCGGCGTT TTATCATCTTCCTCTGCATCCTGCTGCTATGC CTCATCTTCTTGTTGGTTCTTCTGGACTATCA AGGTATGTTGCCCGT TT GTCCTCTAATTCCA GGATCCACACCAGCCGACCATGCCAT AAACCTGCACGACTCCTGCTCAAGGAACCTC TATGT TT CCCTCATGTTGCTGTACAAAACCTA CGGACGGAAACTGCACTTGTATTCCCATCCCC ATCATCTTGGGC TTT CGCAAAATTCCTATGG GAGTGGGCCTCAGTCCGT TT CTCTTGGCTCA GMTCCAAGGAACCTCGTTGGTTGGTT TT CCCCCACTGTCT GGC TTT CAGTTA TATGCATGATGTGGTATTGGGGGCCAAGTCT GTACAACATCTTGAGTCCCT TT ATGCCGCTG TTACCAAIIIICIIIIGICIII GGGTATACATTTAAACCCTCACAAAACAAAAAGATGGGGATA TTCCCTTAACTTCATGGGATATGTAATTGGGA GTTGGGGCACATTGCCGCAGGAACATATTGT ACAAAAAATCAAAATGTGIIIIAGGAAACTTC CTGTAAACCGGCCTATTGATTGGAAAGTATG Petition 870260056387, dated 10 / 06 / 2026, page 153 / 926 145 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence TCAACGAATTGTGGGTC Illi GGGGI 1 1 GCC GCCCCI TT CACGCAATGTGGATATCCTTT TAAGCCTTCAATGCAATGCAATGCATT GAGG^^Cm CTCGCCAACTTACAAGG CCTTCCTAAGTAAACAGTATCTGCACCT T TAC CCCGTTGCTCGGCAACGGCCTGGTCTGTGC CAAGTGT TT GCTGACGCAACCCCCACTGGTT GGGGCTTGGCCATAGGCCATCAGCGCATGC GTGGAGCCTTCTTGTCTCGATCGATC TACTGCGCATCTTCCTGGCCGCTTG TTTT GCT CGCAGCAGGTCTGGGGCAAAACTCATCGGG ACTGACAATTCTGTCGTGCTCTCCCGCAAGT ATACATCC TTT CCATGGCTGCTAGGCTGTGC TGCCAACTGGATCCTGGCGGGACGTCGTCC TTT GTTCTCGATCGTCCGTCCG GACGACCCCTCCCGGGGCCGCTTGGGGCTC TACCGCCCGCTTCTCCGCTTGTTGTACCGAC CGACTACGGGGCGCACCTCTCTCTACGCGG ACTCCCCGTCTGTGCCTTCTCATCTGCCGGA CCGTGTGCACTTCGCTTCACCTCTGCACGTC GCATGGAGACCACC3 90 B 90 dint ATGTCATCCAGATCCCAGAGTCAGGGCCCTG TCC TTT CCTGTTGGTGGCTCCAGTTCAGGAA CAGTGAGCCCTGTTCTGAGTACTGTCTCTGC CACATTGTCAATCTGATTGAGGACTGGGGCC CCTGCACAGAGCATGGTGAACACAGGATCAGGACTCCCAGGACCCCCTGCCAGGGTGACTG GTGGGG TTTT CCTTGTTGACAAAAATCCTCA CAACACCACAGAGTCAAGGCTTGTGGTGGA CTTCTCTCAA TTTT CAAGGGGGAACACAAGG Petition 870260056387, of 10 / 06 / 2026, p. 154 / 926 146 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence GTGTCTTGGCCCAAA1 1 1 GCAGTCCCAAATC TCCAGTCTCTGACCAACCTGTTGTCCTCCAA 1 1 1 1GTCCTGGTTGTCTCTGGATGTCTCTGCT GCCIIIIATCATCTTCCTCTCCTCCTGCTGC CATGCCTCATCTTCTTGTTGGTTCTTCTGGCC TCTCTAGGTATGTTGCCAGATTGTCCTCCAAT TCCAGGATCATCAACAACCAGCAGGACCA TGCAAAACCTGACTGACTGACCTTGACCTT CTCTCATGTTGCTGTACAAAA CCTATGGCAGGAAACTGCAT T TGTATTCCCCA TCCCATCATCTTGGGCTTCAGGAAAATTCCC ATGGGAGTGGGCCTCAGTCCCTTCCCTTGG CTCAGTTCACCAGTGCCA TTT GTTCTGTTGTC AGGAGGGCT TT CCCCCTT GTTGTTGTC' GTTACATGCATGATGTGGTCTTGGGGGCCAA GTCTGTCCAACATCTTGAGTCACT TT ATGCTG CTGTGACCAACTTTCTTTTGTCTTT GGGCATC CAT T TGAACCCTCACAAAAACCAAAAGATGGG GCTATTCCCTCAA TTT CATGGGCTAT ATTGTGCAAAAAATCAAGATGTGT TT CAGGAA ACTTCCTGTGAACAGGCCAATTGACTGGAAA GTCTGTCAGAGAATTGTGGGCTTTTT GGGGT TTGCAGCTCC TTT CACCCAATGTGGCTATCC TGCT TT GATGCCCTTGTATGCCTGCATCCAG GCCAAACAGGCT GCTCACT TT CTCCCCCACTT ACAAGGCCTTCCTCAGCAAACAGTATCTCCA CCT T TACCCTGTTGCAAGGCAGAGGCCTGGT CTGTGCCAAGTGT TT GCTGATGCAACCCCCA CTGGTTGGGGCTTGGCCATTGGCCATCAGA Petition 870260056387, of 10 / 06 / 2026, p. 155 / 926 147 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence GAATGAGAGGTGCCI 1 IGIGICTCCTCTCCC CATCCACACTGCTCATCCCTGGCAGCCTTGC TTT GCAAGGAGGAGCCAACCAA TAGGGACTGACAATTCTGTGGTGCTCTCCAG AAAGTACACCTCC TTT CCTTGGCTGCTGGGC TGTGCAGCCAACTGGATCCTGAGGGGGACT TCC iiiOT Ti ATGTCCCCTCTGCCCTGAATCC TGCAGATGACCCCTCCAGGGGCAGGTTGGACCGGCTTCTTTCGTTAGTT AGACCAACAACAGGGAGGACCTCTCTCTATG CAGATTCCCCCTCTGTTCCTTCTCATCTTCCA GACAGAGTGCACT TT GCTTCTCCTCTGCATG TGGCTTGGAGACCTCCC 91 B Pol300 huCo baixo GC ATGTCTAGCAGAAGCCAGTCCCAGGGACCT ATAGCGAGCCATGTAGCGAGTATTGCCTGTG TCACATCGTGAATCTGATTGAGGATTGGGGA CCATGCACAGAGCACGGAGAGCACCGGATC AGAACCCCTAGGACACCAGCCCCGCGTGACA GGAGGCGTGTTCCTGGTGGATAAGAACCCC CTCGGGGCAATACAAGA GTGTCCTGGCCAAAGT TT GCCGTGCCCAATC TCCAGAGCCTGACAAACCTGCTGTCTTCTAA TCTGAGCTGGCTGTCCCTGGACGTGTCCGC CGCCT TT TACCACCTGCCACTGCACCCTGCCGCCATGCCCCACCTGCTGGTGGGCAGCTCC GGACTGAGCAGATACGTGGCAAGGCTGTCT AGCAATTCTAGAATTATTAATAATCAGCACAG AACAATGCAGAATCTGCATGATTCTTGTAGC Petition 870260056387, dated 10 / 06 / 2026, page 156 / 926 148 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence AGGAATCTGTACGTGAGCCTGATGCTGCTGT ATAAGACATATGGACGCAAGCTGCACCTGTA TTCTCACCTT ATCCCTATGGGCGTGGGACTGTCCCCATTC TGCTGGCCCAGT 1 TACCTCCGCCATCTGCTC TGTGGTGCGGAGAGCCTTCCCACATTGCTG GOCHMCTTACATGCACGATGTGGTGCTGG GCGCCAAATCCGTGCAGCACCTGGAGTCTC TGTATGCCGCCGACTGACTGACTGGA CCTGGGCATCCACCTGAATCCACATAAGACA AAGCGGTGGGGCTATTCTCTGAA TTTT ATGG GCTATGTGATCGGCAGCTGGGGAACCCTGC CACAGGAGCACATTGTGCAGAAGATCAAGAT GTGCT ii CGCAAGCTGCCCGTGAATCGCT ATCGATTGGAGGGAGGGTTCGGAG GGACTGCTGGGATTCGCAGCACCCT TT ACCC AGTGCGGCTACCCAGCCCTGATGCCACTGT ATGCCTGTATCCAGGCCAAACAGGCCTTCAC CMM CCCC T ACA TAT AAGGCTTTT CTGTCTA AGCAGTACCTGCATCTGTATCCAGTGGCAAG GCAGAGGCCAGGCCAGGGTTT AGATGCAACACCAACAGGATGGGGACTGGC AATCGGACACCAGAGGATGAGAGGAGCCTT CGTGAGCCCACTGCCAATTCACACCGCCCA CCTGCTGGCAGCATGCT TT GCAAGGTCCCG CTCTGGAGCAAAGCTGATTGGCACCGATAACAGCGTGGTGCTGTCCAGAAAATACACCAGCT TCCCCTGGCTGCTGGGATGTGCAGCAAATTG GATTCTGAGGGGCACCAGCTTCGTGTATGTG CCTTCCGCCCTGAATCCTGCCGATGATCCAT Petition 870260056387, dated 10 / 06 / 2026, page 157 / 926 149 / 305 Tabela M - Polinucleotídeos que codificam polipeptídeos imunogênicos SEQ ID NO: Genótipo do HBV Nome Sequência de polinucleotídeos CTCGAGGCAGACTGGGACTGTATAGGCCAC TGCTGAGACTGCTGTATAGGCCTACCACAGG CAGAACATCCCTGTATGCCGACAGCCCATCC GTGCCCTCTCACCTGCCAGATAGAGTGCATT TCGCAAGCCCACTGCATGTGGCATGGAGGC CACCC 92 B Pol300 ori_del CpG ATGTCTTCAAGATCCCAGAGTCAGGGCCCTG TACT 1 1 CCTGCTGGTGGCTCCAGTTCAGGAA CAGTGAGCCCTGCTCTGAATACTGTCTCTGC CATATTGTCAATCTTATAGAAGACTGGGGAC CCTGTACTGAACATGGAGAACATAGGATCAG GACTCCTAGGACCCCTGCTAGAGTTACAGG GGGGGTTTTT CTTGTTGACAAAAATCCTCAC AATACCACAGAGTCTAGACTTGTGGTGGACT TCTCTCAAT T T TCTAGGGGGAACACCAGGGT GTCTTGGCCAAAA T T T GCAGTCCCAAATCTC CAGTCACTCACCAACCTGTTGTCCTCCAAT T T GTCCTGGTTATCCCTGGATGTGTCTGCAGCC TTTT ATCATCTTCCTCTGCATCCTGCTGCTAT GCCTCATCTTCTTGTTGGTTCTTCTGGACTAT CAAGGTATGTTGCCAGGTTGTCCTCTAATTC CAGGATCATCAACAACCAGCACAGGACCATG CAAAACCTGCATGACTCCTGCTCAAGGAACC TCTATG T T T CCCTCATGTTGCTGTACAAAACC TATGGAAGGAAACTGCACTTGTATTCCCATC CCATCATCTTGGGCT T TAGAAAAATTCCTATGGGAGTGGGCCTCAGTCCCT TT CTCTTGGCTC AGTTTACTAG'T GCCAT TT GTTCAGTGGTTAGA AGGGCT TT CCCCCACTGTCT GGCT TT CAGTT ATATGCATGATGTGGTATTGGGGGCCAAGTC Petition 870260056387, of 10 / 06 / 2026, p. 158 / 926 150 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence TGTACAACATCTTGAGTCCCI 1 IATGCTGCTG TTACCAAIIIICIIIIGICIIIGGTATACATT TAAACCCTCAGAGAGAGAGAGA TTCCCTTAACTTCATGGGATATGTAATTGGGA GTTGGGGCACATTTGCCTCAGGAACATATTGT ACAAAAAATCAAAATGTGTTTT AGGAAACTTC CTGTAAACAGGCCTATTGATTGGAAAGTATG TCAAAGAATTGTGGGTCTTTT GGGG TTT GCA GCCCCATGTTGTTGTTGTT TT ATATGCATGTATACAAGCAAAA CAGGCTTTTACTTT CTCCCCAACTTACAAGG CCTTCCTAAGTAAACAGTATCTGCACCT T TAC CCTGTTGCTAGGCAAAGGCCTGGTCTGTGC CAAGTGT TT GCTGATGCAACCCCCACTGGTT GGGGCTTGGCC GTGTCTCCTCTGCCTATCCA TACTGCCCATCTTCCTGGCAGCTTGIIII GCT AGGAGCAGGTCTGGGGCAAAACTCATTGGG ACTGACAATTCTGTTGTGCTCTCCAGAAAGT ATACATCC TTT CCATGGCTGCTAGGCTGTGC TGCCAACTGGATCCTGAGGGTTTC ATGTCCCTTCAGCACTGAATCCTGCTG ATGACCCCTCCAGGGGCAGATTGGGGCTCT ACAGGCCCCTTCTCAGGTTGTTGTACAGACC CACTACTGGGAGAACCTCTCTCTATGCAGAC TCCCCCTCTGTGCCTTCATCTGCCTGACAGGGTGCACT TT GCTTCACCTCTGCATGTTGC ATGGAGACCACCT 93 B Pol300 IDT ATGAGTTCCCGATCACAGAGTCAGGGGCCC GTCC TTTCAT GTT GGT GGCT T CAGT TT CGAA Petition 870260056387, of 10 / 06 / 2026, p. 159 / 926 151 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence ACTCCGAGCCATGTTCTGAGTATTGTCTCTG CCACATTGTGAATCTTATTGAAGACTGGGGC CCCTGACCGAGCACCGACCGA CGGACACCTCGAACGCCAGCAAGAGTGACG GGCGGAGTGTTCCTCGTCGACAAGAATCCA CACAACACGACGGAGAGTAGATTGGTCGTTG Alli CAGi CAA Illi CAAGAGGCAATACACGA Gill CTTGGCCGAAATTCGCCGTACCGAATC TGCAATCCTTGACAAA lll GCTTAGTTCGTGIgtci ccgccg Clll CTATCACTTGCCCCTTCACCCAGCCGC GATGCCGCATCTCTTGGTGGGCAGCTCTGG ACTTAGTAGATACGTAGCTAGACTCAGTTCTA ACTCACGGATAATAAATAACCAACATCGCAC TATGCAGAACCTGCATGATTCTTGTTCCCGG AACTTGTATGCTTTGTTGTTGTT AACTTATGGGCGAAAGCTTCATCTGTATAGC CATCCGATTATATTGGGIIIIAGGAAAAATTCC TATGGGTGTTGGCTTGAGCCC Illi CTGCTG GCGCAAI I IACTTCAGCTATCTGCTCAGTAG TACGCCGGGCGI II CCCCAIIGICIIGCCIII CTCATACATGCCATGGGTTGGTT AAGTCTGTACAACACCTTGAGAGI I IGTATG CCGCCGTAACTAAI I ICCTTCTCTCTCTCGG GATCCATCTTAACCCTCCAAAACGAAGAGG TGGGGTTATTCTCTGAAI II CATGGGATATGTTATCGGGTCTTGGGGAACGCTGCCTCAGGA ACACATCGTCCAGAAAATCAAGATGTGIIIC AGAAAGTTGCCAGTGAACAGACCGATAGATT GGAAGG III GCCAAAGAATTGTTGGCTTGTT Petition 870260056387, of 10 / 06 / 2026, p. 160 / 926 152 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence GGGATTCGCAGCCCCATTCACACAGTGCGG GTATCCGGCIIIGAI GCCCCI 1 1ATGCTTGT CGACTTACAAAGCAI IICII ICTAAGCAGTAT CTCCATCI I IACCCTGTCGCTCGACAGCGGC CGGGGCI II GCCAGG IIII CGCAGACGCAA CCCCAACTGGTTGGGGTCTTGCGATCGGCC ACCAGAGGATGGCGGTGCATTCGTGTCCCCCGACCGCCGCCTTGCCTT GGCGTGCTTCGCTCGAAGTAGAAGCGGGGC TAAATTGATCGGCACCGGACAATTCAGTCGTG TTGTCACGCAAATATACCTCC III CCCTGGTT GCTCGGTTGCGCAGCAAACTGGATACTTCG GGGAACTAGIIICGIIIATGTGCCCTCTGCT CTCAACCCCGGAAGCAGCCAGGCCGTGCCTT IACCGCCCATTGCTCAGGC TGCI I IACCGGCCTACCACTGGGAGAACAAG CTTGTACGCCGACAGCCCGAGCGTCCCGTC TCATCTGCCCGACAGAGTTCCACI II GCGAGT CCATTGCACGTCGCTTGGCGCCCGCCG 94 B Pol300_I DT_Cp Gdel ATGAGACCAGTCAGTCAGTCAGTCAGTC IIICAIGIIGGIGCI I CAGI I IAGAAA CTCAGAGCCATGTTCTGAGTATTGTCTCTGC CACATTGTGAATCTTATTGAAGACTGGGGCC CCTGCACAGAGCATGGAGAGCACAGAATAAGGACACCTAGAACCCCAGCAAGAGTGACAG GTGGAGTGTTCCTGGTAGACAAGAATCCACA CAACACAACTGAGAGTAGATTGGTGGTTGAT TTCAGTCAA IIII CAAGAGGCAATACAAGAGT TTCTTGGCCAAAAI II GCTGTACCCAATCTGC Petition 870260056387, of 10 / 06 / 2026, p. 161 / 926 153 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence AATCCTTGACAAA1 1 1 GCTTAGTTCTAAIIIG TCTTGGCIIICICIAGAIGIIICIGCAGCI II CCTCATCTCTTGGTGGGCAGCTCTGGACTTA GTAGATATGTAGCTAGACTCAGTTCTAACTCA AGGATAATAAATAACCAACATAGGACTATGC AGAACCTGCATGATTCTTGTTCCAGGAACTT GTATGTCTCCTTGATGTTGTTGTATAAAACTT ATGGGAGATAAGCTTCATCCATCC TATTATATTGGGIIIIAGGAAAATTCCTATGG GTGTTGGCTTGAGCCC IIII CTGCTGGCCCA AI I IACTTCAGCTATCTGCTCAGTAAGGA GGGCCI II CCCCAIIGICIIGCIII CTCATAC ATGCATGATGTAGTACTTGGGGCCAAGTCTG CCTTCTCTCTCTTGGGATCCATC TTAACCCTCCAAAACCAAGGTGGGGTTA TTCTCTGAAI II CATGGGATATGTTATAGGGT CTTGGGGAACCCTGCCTCAGGAACACATGT CCAGAAAATCAAGATGI I ICAGAAAGTTG CCAGTGAACACCAGAGAG GCCAAAGAATTGTTGGCTTGTTGGGAIIIGC AGCCCCATTCACACAGTGTGGGTATCCTGCT TTGATGCCCCI I IATGCTTGTATCCAGGCAA AACAGGCATTCACC IIII CACCCACTTACAAA GCA IIICIIICIAAGCAGIAIC CCAICIIIA CCCTGTGGCTAGACAGAGGCCAGGGCIIIG CCAGG IIIIII GCAGATGCAACCCCAACTGGT TGGGGTCTTGCAATTGGCCACCAGAGGATG AGAGGTGCAI II GTGTCCCCCACTCCCAATCC Petition 870260056387, of 10 / 06 / 2026, p. 162 / 926 154 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence ATACTGCCCACTTGCTGGCAGCTTGCTTTGC TAGAAGTAGAAGTGGGGCTAAATTGATTGGCAGCAATGTCAGTTCATTGATTGATTGATTGATTGATT CCCTGGTTGCTTGGTTGTGC AGCAAACTGGATACTTAGGGGAACTAGTTTT GTM ATGTGCCCTCTGCTCTCAACCCTGCAG ATGATCCTTCAAGGGGAGCTGGGTC OLD CAGGCCATTGCTCAGGCTGCT TT ACAGGCCT ACCACTGGGAGAACCAAGCAGAGCCATT GCCCCAGTGTCCCCTCTCATCTGCCTGACAG AGTTCACT TT GCAAGTCCATTGCATGTTGCTT GGAGACCTCCA 30 D ΡοΙΔ1 ATGCCCCTGAGCTACCAACACTTCAGGAGAC TGCTGCTGCTGGATGATGAGGCAGGCCCTC TGGAGGAGGAGGCTGGCT AGGGCCTGAACAGGAGGGTGGCTGAGGACC TGAACCTGGGCAACCTGAATGTGAGCATCCC TTGGACCCACAAAGTGGGCAACTTCACAGGC CTGTACAGCAGCACTGTGCCTGTGTTCAACC CCCACTGGAAGACACCCAGCTTCCCCAACAT CCACCTGCACCAGGACAGAGCAGCAGTTCAAGTTT GTGGGCCCCCTGACAGTCAAT GAGAAGAGGAGGCTCCAGCTGATCATGCCA GCCAGGTTCTACCCCAATGTGACCAAGTACC TCCCCCTGGACAAGGGCATCAAGCCTTACTA TCCAGAGCACCTGGTGAACCACTACTTCCAG ACCAGACACTACCTGCACACTGTGGAAGGGACTCAGGCATCCTGTACAAGAGGGAGACCACAC ACAGTGCCTCCTTCTGTGGCAGCCCCTACTC CTGGGAGCAGGAGCTGCAACATGGAGCTGA Petition 870260056387, dated 10 / 06 / 2026, page 163 / 926 155 / 305 Tabela M - Polinucleotídeos que codificam polipeptídeos imunogênicos SEQ ID NO: Genótipo do HBV Nome Sequência de polinucleotídeos GTCCTTCCACCAGCAGTCCAGTGGCATCCTG AGCAGGCCCCCTGTGGGCAGCGAGCTGCAC AACCTGCCCCCCAACTCTGCCAGATCCCAGT CTGAGAGGCCAGTGTTCCCTTGCTGGTGGC TCCAGTTCAGGAACAGCAAGCCCTGCTCAGA CTACTGCCTGAGCCACATTGTGAACCTGCTG GAGGACTGGGGCCCCTGTGCAGAGCATGGG GAGCACCACATCAGAATCCCCAGGACCCCT GCCAGGGTGACAGGAGGGGTGTTCCTGGTG GACAAGAACCCCCACAACACTGCAGAGTCCA GGCTGGTGGTGGACTTCTCCCAGTTCAGCA GGGGCAACTACAGAGTCTCCTGGCCAAAGTT TGCTGTGCCCAACCTCCAGAGCCTGACAAAC CTGCTGAGCAGCAACCTGTCCTGGCTCTCCC TGGATGTGAGTGCAGCCTTCTATCACCTGCC CCTGCACCCAGCAGCCATGCCACACCTGCT GGTGGGCTCCAGTGGCCTGTCCAGGTATGT GGCCAGGCTCTCCTCCAACTCCAGGATCTTC AACTATCAGCATGGCACCATGCAGAACCTGC ATGACAGCTGCTCCAGGAACCTGTATGTGTC CCTGATGCTGCTCTATCAGACC 1 1 1GGCAGG AAGCTGCACCTGTACAGCCACCCCATCATCC TGGGGTTCAGGAAGATCCCCATGGGTGTGG GCCTGTCCCCCTTCCTGCTGGCCCAGTTCAC CAGTGCCATCTGCTCAGTGGTGAGGAGGGC CTTCCCACACTGCCTGGCCTTCTCTTACATG CATGATGTGGTCCTGGGTGCCAAGTCTGTGCAGCACCTGGAGAGCCTGTTCACAGCTGTGA CAAACI 1 1 CTCCTGAGCCTGGGCATCCACCT GAACCCCAACAAGACCAAGAGGTGGGGTTA Petition 870260056387, dated 10 / 06 / 2026, page 164 / 926 156 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence TTCACTGCACTTCATGGGCTATGTGATTGGC TGCTATGGCTCTCTGCCACAGGACCACATCA GCCAGTGAACAGGCCAATTGACTGGAAGGT GTGCCAGAGGATTGTGGGCCTGCTGGGCTT TGCAGCCCCCTTCACCCAGTGGCTACCCT GCCCTGATGCCCCTGTATGCCTGCATCCAGA GCAAGCAGGCCTTCACC Illi CCCCCACTTA CAAGGCCTTCCTGCAAGCAGCGA CTGTACCCTGTGGCCAGGCAGAGACCTGGG CTGTGCCAGGTG TTT GCAGATGCCACCCCCA CAGGATGGGGACTGGTCATGGGACACCCAGA GGATGAGGGGCACCTTCAAGGCACCCCTGC CCATTCCACACAGCCCACCTGCTGGCTGCGCT GCAGGAGGAGCCAGGGCG TCCTGGGGCACAGACAACTCTGTGGTGCTGA GCAGGAAGTACACATCCTTCCCCTGGCTGCT GGGATGTGCAGCCAACTGGATCCTGAGGGG CACCAGCT TT GTGTATGTGCCCTCTGCCCTC AACCCTGCAGATGATCCAAGCAGGGGCAGG CTGGGACTGCCAGCTGACTGACTGACT CCCTTCAGGCCCACCACTGGCAGGACCAGGC CTGTATGCTGACTCCCCATCTGTGCCCTCCC ACCTGCCTGACAGAGTGCACT TT GCCTCCCC ACTGCATGTGGCCTGGAGGCCCCCA 31 D ΡοΙΔ3TGAGGAGGAGCTGCCCAGGCTGGCAGATG AGGGCCTGAACAGGAGGGTGGCTGAGGACC TGAACCTGGGCAACCTGAATGTGAGCATCCC Petition 870260056387, dated 10 / 06 / 2026, page 165 / 926 157 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence TTGGACCCAAAGTGGGCAACTTCACAGGC CTGTACAGCAGCACTGTGCCTGTGTTCAACC CCACCTGCACCAGGACATCATCAAGAAGTGT GAGCAGI 1 1 GTGGGCCCCCTGACAGTCAAT GAGAAGAGGAGGCTCCAGCTGATCATGCCA GCCAGGTTCTACCCCAATGTGACCAAGTACC TCCCCCTGGACAAGGGCATCAAGCCTTACTA TCCAGAGCACCTGACCTAGTTGACCAGCC ACCAGACACTACCTGCACACACCTGTGGAAGG CAGGCATCCTGTACAAGAGGGAGACCACAC ACAGTGCCTCCTTCTGTGGCAGCCCCTACTC CTGGGAGCAGGAGCTGCAACATGGATGCTG GTGGCTCCAGTTCAGGAACAGCAAGCCCTG CTCAGACTACTGACCTTGAGCTTGAGCCA CTGCTGGAGGACTGGGGCCCCTGTGCAGAG CATGGGGAGCACCACATCAGAATCCCCAGG ACCCCTGCCAGGGTGACAGGAGGGGTGTTC CTGGTGGACAAGAACCCCCACAACACTGCA GAGTCCAGGCTGGTGGTGGACTTCCCAG GCTGTGCCCAACCTCCAGAGCC TGACAAACCTGCTGAGCAGCAACCTGTCCTG GCTCTCCCTGGATGTGAGTGCAGCCTTCTAT CACCTGCCCCTGCACCCAGCAGCCATGCCA CACCTGCTGGTGGGCTCCAGTGGCCTGTCC AGGTATGTGGCCAGGCTCCTCCAACTCCAGGATCTTCAACTATCAGCATGGCACCATGCA GAACCTGCATGACAGCTGCTCCAGGAACCT GTATGTGTCCCTGATGCTGCTCTATCAGACC Petition 870260056387, dated 10 / 06 / 2026, page 166 / 926 158 / 305 Tabela M - Polinucleotídeos que codificam polipeptídeos imunogênicos SEQ ID NO: Genótipo do HBV Nome Sequência de polinucleotídeos 1 1 1GGCAGGAAGCTGCACCTGTACAGCCACC CCATCATCCTGGGGTTCAGGAAGATCCCCAT GGGTGTGGGCCTGTCCCCCTTCCTGCTGGC CCAGTTCACCAGTGCCATCTGCTCAGTGGTG AGGAGGGCCTTCCCACACTGCCTGGCCTTC TCTTACATGCATGATGTGGTCCTGGGTGCCA AGTCTGTGCAGCACCTGGAGAGCCTGTTCAC AGCTGTGACAAACT 1 1 CTCCTGAGCCTGGGC ATCCACCTGAACCCCAACAAGACCAAGAGGT GGGGTTATTCACTGCACTTCATGGGCTATGT GATTGGCTGCTATGGCTCTCTGCCACAGGAC CACATCATCCAGAAGATCAAGGAGTGCTTCA GAAAGCTGCCAGTGAACAGGCCAATTGACTG GAAGGTGTGCCAGAGGATTGTGGGCCTGCT GGGCT T T GCAGCCCCCTTCACCCAGTGTGG CTACCCTGCCCTGATGCCCCTGTATGCCTGC ATCCAGAGCAAGCAGGCCTTCACC TTTT CCC CCACTTACAAGGCCTTCCTGTGCAAGCAGTA CCTGAACCTGTACCCTGTGGCCAGGCAGAG ACCTGGGCTGTGCCAGGTGT T T GCAGATGC CACCCCCACAGGATGGGGACTGGTCATGGG ACACCAGAGGATGAGGGGCACCTTCAAGGC ACCCCTGCCCATCCACACAGCCCACCTGCT GGCTGCCTGCT T T GCCAGGAGCAGGAGTGG GGCCAACATCCTGGGCACAGACAACTCTGT GGTGCTGAGCAGGAAGTACACATCCTTCCCC TGGCTGCTGGGATGTGCAGCCAACTGGATCCTGAGGGGCACCAGCT TT GTGTATGTGCCCT CTGCCCTCAACCCTGCAGATGATCCAAGCAG GGGCAGGCTGGGACTGTACAGGCCACTGCT Petition 870260056387, of 10 / 06 / 2026, p. 167 / 926 159 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence CAGACTGCCCTTCAGGCCCACCACTGGCAG GACCAGCCTGTATGCTGACTCCCCATCTGTG CCTCCCCACTGCATGTGGCCTGGAGGCCCC CA 32 D Pol300 ATGTCTGCCAGATCCCAGTCTGAGAGGCCA GTGTTCCCTTGCTGGTGGCTCCAGTTCAGGA ACAGCAAGCCCTGCTCAGACTACTGCCTGAG CCACATTGTGAACCTGCTGGAGGACTGGGGGCCGGGAGGAGGA CAGAATCCCCAGGACCCCTGCCAGGGTGAC AGGAGGGGTGTTCCTGGTGGACAAGAACCC CCACAACACTGCAGAGTCCAGGCTGGTGGT GGACTTCTCCCAGTTCAGCAGGGCAACTAC AGAGTCTCCTGGCCAAAGT ii GCTGTGCCCA ACCTCCAGACCTTGACCTTGCAGACTGA GCAACCTGTCCTGGCTCTCCCTGGATGTGAG TGCAGCCTTCTATCACCTGCCCCTGCACCCA GCAGCCATGCCACACCTGCTGGTGGGCTCC AGTGGCCTGTCCAGGTATGTGGCCAGGCTC TCCTCCAACTCCAGGATCTTCAACTATCAGC ATGGCCACC CTCCAGGAACCTGTATGTGTCCCTGATGCTG CTCTATCAGACC TTT GGCAGGAAGCTGCACC TGTACAGCCACCCCATCATCCTGGGGTTCAG GAAGATCCCCATGGGTGTGGGCCTGTCCCC CTTCCTGCTGGCCCAGTTCACCAGTGCCATCTGCTCAGTGGTGAGGAGGGCCTTCCCACAC TGCCTGGCCTTCTCTTACATGCATGATGTGG TCCTGGGTGCCAAGTCTGTGCAGCACCTGG Petition 870260056387, dated 10 / 06 / 2026, page 168 / 926 160 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence AGAGCCTGTTCACAGCTGTGACAAACIIICI CCTGAGCCTGGGCATCCACCTGAACCCCAA CAAGACCAAGGTCAGGGGGCTTTA TTCATGGGGCTATGTGATTGGCTGCTATGGCT CTCTGCCACAGGACCACATCATCCAGAAGAT CAAGGAGTGCTTCAGAAAGCTGCCAGTGAAC AGGCCAATTGACTGGAAGGTGTGCCAGAGG ATTGTGGGCCTGCTGGGCT TT GCAGCCCCCGTCACCCAGTGCTGCTGCTGCCGCT CCCTGTATGCCTGCATCCAGAGCAAGCAGG CCTTCACC HTT CCCCCACTTACAAGGCCTT CCTGTGCAAGCAAGCAGTACCTGAACCTGTACCCT GTGGCCAGGCAGAGACCTGGGCTGTGCCAG GTGT TTGCAGATGCCACCCCCACAGGGGGGGGGGGGTCAGGGAGGGAGGGA GGCACCTTCCAAGGCACCCCTGCCCATCCAC ACAGCCCACCTGCTGGCTGCCTGC TT T GCCA GGAGCAGGAGTGGGGCCAACATCCTGGGCA CAGACAACTCTGTGGTGCTGAGCAGGAAGTA CACATCCTTCCCCTGGCTGCTGGGATGTGCA GTGTATGTGCCCTCTGCCCTCAACCCTGCAG ATGATCCAAGCAGGGGCAGGCTGGGACTGT ACAGGCCACTGCTCAGACTGCCCTTCAGGC CCACCACTGGCAGGACCAGCCCTGTATGCTG ACTCCCCATCTGTGCCCCCACCTGCCTGA CAGAGTGCCACTGCCTGGAGGCCCCCA 33 B / C NucleosAg ATGGACATTGACCCCTACAAGGAGT TT GGGG CCAGTGTGGAGCTGCTGTCIIII CTGCCATC Petition 870260056387, of 10 / 06 / 2026, p. 169 / 926 161 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence TGACTTCTTCCCCAGTGTGAGGGACCTGCTG CACACAGCCCTGAGGCAGGCCATCCTCTGC TGGGGGGAGCTGATGAACCTGGCCACCTGG GTGGGCTCCAACCTGGAGGACCCTGCCTCA AGGGAGCTGGTGGTCAGCTATGTCAATGTGA ACATGGGCCTCAAGATCAGGCAGCTGCTGT GGTTCCACATCCTGATC1GTCAG11 GGAGACAGTCCTGGAGTACCTGGTGAGC1 1 1 GGGGTGTGGATCAGGACCCCCCCTGCCTAC AGGCCCCCCAATGCTCCCATCCTGTCCACCC TGCCAGAGACCACTGTGGTCAGGAGAAGGG GCAGGTCCCCCAGGAGGAGAACCCTCTCTCAGGAGGAGGACCGAGGACCAGGACCTC GGAGGAGGAGCCAGAGCAGAGAGTCTCAGT GCATGGAGAGCACCACATCAGGCTTCCTGG GCCCCCTGCTGGTGCTCCAGGCAGGCTTCT TTCTGCTGACCAGGATTCTGACCATCCCCCA GTCCCTGGACAGCTGGTGGACCTCCCTGAA 1 III CTGGGCCGGGCTGCTGTC CCAGAACTCTCAGTCTCCCACCTCGAATCAC TCACCAACCAGCTGTCCCCCCATCTGTCCTG GCTACAGGTGGATGTGCCTGAGGAGATTCAT CATCTTCCTGTGCATCCTGCTGCTGTGCCTG ATCT ii CTGCTGGTGCTGCTGGACTACCAGG GCATGCTCAGCCAGCTGCCGCTGCAGCTCCACCACATCCACAGGACCTTGCAA GACATGCACCACACCAGCCCAGGGCACCAG CATGTTCCCCTCCTGCTGTTGCACCAAGCCA Petition 870260056387, dated 10 / 06 / 2026, page 170 / 926 162 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide sequence ACAGATGGCAACTGCACATGCATTCCCATCC CCTCCAGCTGGGCCI GTCTCTTCTGGTGCCC IIIGI GCAGIGGIII GTGGGCCTGTCCCCTACAGTGTGGCTGAGT GTCATCTGGATGATGTGGTACTGGGGCCCCT CCCTGTACAACATCCTCTCTCCCII ICIGCCI ^G^G^AAI^^ IIII GCCTGTGGGTGT ACAIC 3AC 34o- P2A AIGGACAIIGACCCCIACAAGGAGI II GGGG CCAGTGTGTGGAGCTGCTGTCIIII CIGCCAIC TGACπCπCCCCAGTGTGAGGGACCTGCTG GACACIGCCICAGCACIGIACAGAGAGGCC CIGGAGAGCCCAGAGCACIGCICCCCCCAC CACACAGCCCTGAGCCAGCCTCGCCCT ΓGGGGGGAGCTGATGAACCTGGCCACCTGG GTGGGCTCCAACCTGGAGGACCCTGCCTCA AGGGAGCTGGTGGTCAGCTATGTCAATGTGA ACATGGGCCTCAAGATCAGGCAGCTGCTGT GGIICCACAICCIGCCIGCCIGACC III GGAGACCAC II GGAGACCAGGIGGACC GGGGTGTGGATCAGGACCCCCCCTGCCTAC AGGCCCCCCAATGCTCCCATCCTGTCCACCC 1GCCAGAGACC ACTGTGGTCAGGAGAAGGGGCAGGTCCCCC AGGAGGAGAACCCCCICICCCAGGAGGAGGG AGAAGCCAGICCCCCAGGAGGAGGAGGAGGAGCCAGAGCAGAGAGTCTCAGTGCGGCAGTGGG GCAACCAACπCAGCCTCCTGAAACAGGCAG Petition 870260056387, dated 10 / 06 / 2026, page 171 / 926 163 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence GGGATGTGGAGGAAAACCCAGGCCCCGAGA GCACCACATCAGGCTTCCTGGGCCCCCTGC TGGTGCTCCTTGGCCCT1 CAGGATTCTGACCATCCCCCAGTCCCTGGAC AGCTGGTGGACCTCCCTGAAT TT TCTGGGGG GGGCCCCTACCTGTCCTGGCCAGAACTCTC AGTCTCCCACCTCGAATCACTCACCAACCAG CTGTCCCCCCATCTGTCCTGGCTACAGGTGG GCATCCTGCTGCTGTGCCTGATCT TT CTGCT GGTGCTGCTGGACTACCAGGGCATGCTGCC AGTGTGCCCTCTCATCCCAGGCAGCTCCACC ACATCCACAGGACCTTGCAAGACATGCACCA CACCAGCCCAGGGCACCAGCATGTTCCCCT CCTGCTGTTGCCAGCCAGCCAGCAGCCAA CTGCACATGCATTCCCATCCCCTCCAGCTGG GCCT TT GCCAGG TTT CTGTGGGAGTGGGCC AGTGTGAGA TTTT CCTGGCTGTCTCCTTCTGG TGCCC TTTGT GCAGTGGTTT GTGGGCCTGTC CCCTACAGTGTGGCTGAGTGTCATCTGGAGGATGGACCTA TCCTCTCTCCC TTT CTGCCTCTGCTGCCAAT CTTCTTTT GCCTGTGGGTGTACATC 35 D / D NucleosAg ATGGACATTGACCCCTACAAGGAGT TT GGGG CCAGTGTGGAGCTGCTCTCCTTCCTGCCCTC AGACTTCT TT CCCAGTGTGAGGGACCTTGGACCTTGACACAGCCTCTGCCCTCTACAGAGAGGCC CTGGAGAGCCCAGAGCATTGCTCCCCCCAC CACACAGCACTGAGGCAGGCCATCCTGTGC TGGGGGGAGCTCATGAACCTGGCCACCTGG Petição 870260056387, de 10 / 06 / 2026, pág. 172 / 926 164 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence GTGGGTGTCAACCTGGAGGACCCAGCTTCC AGGGATCTGGTGGTCAGCTATGTGAACACAA ACATGGGCCAGCTAGCTAGCTAGCT GTTCCACATCTCCTGCCTGACC 1 1 1GGCAGG GAGACTGTGCTGGAGTACCTGGTGAGCTTTG GAGTGTGGATCAGGACCCCACCTGCCTACA GGCCCCCCAATGCCCCCATCCCTGTCCACCC TGCCTGAGACCACAGTGGTGAGGAGGAGGGGGGAGGCCCCGATTGCCGACC CCAGGAGGAGGAGGAGTCAGTCTCCCAGGA GGAGGAGGAGCCAGCAGAGAGAGTCCCAGT GTATGGAGAACATCACCTCTGGCT TT CTGGG ACCCCTGCTGGTGCTCCAGGCAGGCTTTTTC CTGCTGACCAGGATCCTGACCATCCCTCAGA GCCTGGACTGACTGCTGACCAT TCTTGGGGGGCACCACTGTGTGCCTGGGACA GAACTCCCAGTCTCCCACCTCCAACCACAGC CCAACATCCTGTCCCCCCATCTGCCCAGGCT ACAGGTGGATGTGCCTGAGGAGGTTCATCAT CTTCCTGTTCATCCCTGCTGCTGTGCCTGATC TTT CTGCTGGCTGCCATGGCTGGCTGCT TGCTGCCAGTGTGCCCACTGATCCCAGGCA GCTCCACCACAAGCACAGGACCTTGCAGGA CATGCACCACACCTGCCCAGGGCACTTCCAT GTACCCATCTTGCTGTTGCACCAAGCCATCT GATGGCAATTGCACCTGCATCCCCATCCCCCT CAAGCTGGGCCT TT GGCAAGGTTCGTGTCAGTGGGCAAGTGCCAGATTCTCTTGGCTGAG CCTGCTGGTCCC TTTTGT GCAGTGGTTT GTG GGGCCTGAGCCCCACTGTGTGGCTGTCTGTG Petition 870260056387, dated 10 / 06 / 2026, page 173 / 926 165 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence ATCTGGATGATGTGGTACTGGGGCCCCTCC CTGTATTCAATCCTGAGCCC Illi CTGCCACT GCTGCCCTTCCTTGGTTGGGGGGG6 D / D Nucleo- P2AsAg ATGGACATTGACCCCTACAAGGAGT TT GGGG CCAGTGTGGAGCTGCTCTCCTTCCTGCCCTC AGACTTCT TT CCCAGTGTGAGGGACCTGCTT GACACAGCCTCTGCCCTCTACAGAGAGGCC CTGGAGAGCCCAGCCCACCCCACTTGCCTT CACACAGCACTGAGGCAGGCCATCCTGTGC TGGGGGGAGCTCATGAACCTGGCCACCTGG GTGGGTGTCAACCTGGAGGACCCAGCTTCC AGGGATCTGGTGGTCAGCTATGTGAACACAA ACATGGGCCTCAAGTTCAGGCAGCTGCTCTG GAGACTGTGCTGGAGTACCTGGTGAGCTTTG GAGTGTGGATCAGGACCCCACCTGCCTACA GGCCCCCCAATGCCCCCATCCTGTCCACCC TGCCTGAGACCACAGTGGTGAGGAGGAGGGGGGAGGTCCCCCAGAAGGAGGACCCCTTTCTCAGGAGGAGGAGGAGTCGAGTCGA GGAGGAGGAGCCAGGCAGCAGAGAGTCCCAGT GTGGCAGTGGGGCAACCAACTTCAGCCTCC TGAAACAGGCAGGGGATGTGGAGGAAAAACC CAGGCCCCGAGAACATCACCTCTGGCTTTCT GGGACCCCTGCTGGTGCTCCAGGCAGGCTT TTT CCTGCTGACCGGACCATCCATCCTTCAGAGCCTGGACTCCTGGTGGACATCTCTGA ATU TCTTGGGGGCACCACTGTGTGCCTGGG ACAGAACTCCCAGTCTCCCACCTCCAACCAC Petition 870260056387, of 10 / 06 / 2026, p. 174 / 926 166 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence AGCCCAACATCCTGTCCCCCCATCTGCCCAG GCTACAGGTGGATGTGCCTGAGGAGGTTCA CTGCTGGTGCTCCTGGACTATCAG GGCATGCTGCCAGTGTGCCCACTGATCCCA GGCAGCTCCACCACAAGCACAGGACCTTGC AGGACAIGCACCACACCIGCCCAGGGCACI TCCATGTACCCATCCTTGCTGTTGCACCAAGC CATCTGATGGCAATTGCATCCATGCATCCATCCATGCCAGCCATGCCAGGCCATGCCATGCCATGC TGGGAGTGGGCAAGTGCCAGATTCTCTTGG CTGAGCCTGCTGGTCCCIIII GTGCAGTGGT TTGTGGGCCTGAGCCCCACTGTGTGGCTGT CTGTGATCTGGATGATGGGTACTGGGGCC CCTCCCTGTATTCAATCCTGAGCCC IIII CIG CCACTCCATGCCIGGGGCC 37 D / D iNucleo -P2AsAg AIGGACAIIGACCCCIACAAGGAGI II GGGG CCAGTGTGGAGCTGCTGTCIIII CIGCCAIC TGACπCπCCCCAGTGTGAGGGACCTGCTG CACACAGCCCTGAGGCAGGCCATCCTCTGC ΓGGGGGGAGCTGATGAACCTGGCCACCTGG GTGGGCGTCAACCTGGAGGACCCTGCCTCA AGGGACCTGGTGGTCAGCTATGTCAATACGA ACATGGGCCTCAAGTTCAGGCAGCTGCTGTGGIICCACAICICCIGCCIGACC III GGCAG GGAGACAGICCIGGAGIACCIGGIGAGCI II GGGGTGTGGATCAGGACCCCCCCTGCCTAC Petition 870260056387, of 10 / 06 / 2026, p. 175 / 926 167 / 305 Table M - Polynucleotides Encoding Immunogenic Polypeptides SEQ ID NO: HBV Genotype Name Polynucleotide Sequence AGGCCCCCCAATGCTCCCATCCTGTCCACCC TGCCAGAGAGACCACTGTGGTCAGGAGAAGGG GCAGGTCCCGACCGATCGATCCCG CCAGGAGGAGGAGAAGCCAGTCCCCCAGGA GGAGGAGGAGCCAGCAGAGAGAGTCTCAGT GCGGCAGTGGGGCAACCAACTTCAGCCTCC TGAAACAGGCAGGGGATGTGGAGGAAAACC CAGGCCCCGAGAACATCACATCAGGCTTCCT GGGCCCCCTGCTGCTGCTGCCTT CTGCTGACCAGGATTCTGACCATCCCC CAGTCCCTGGACAGCTGGTGGACCTCCCTG AAHH CTGGGGGGACCACTGTCTGTCTTG GCCAGAACTCTCAGTCTCCCACCTCGAATCA CTCACCAACCAGCTGTCCCCCCATCTGTCCT GGCTACAGGTGGGGGGAGGAGGTC ATCATCTTCCTGTTCATCCTGCTGCTGTGCCT GATCT TT CTGCTGGTGCTGCTGGACTACCAG GGCATGCTGCCAGTGTGCCCTCTCATCCCA GGCAGCTCCACACATCCACAGGACCTTGC AGGACATGCACCACACCAGCCCAGGGCACC AGCATGTACCCCTTTCCCAGCCAGGCC CATCAGATGGCAACTGCACATGCATTCCCAT CCCCTCCAGCTGGGCCT TT GGCAAGT TT CTG TGGGAGTGGGCCAGTGCGAGAT TT TCCTGG CTGTCTCCTTCTGGTGCCC TTT GTGCAGTGGTCCTCCCTGTACAGCATCCTCTCTCCCTTTCT GCCTCTGCTGCCAATCTTTTTT GCCTGTGG GTGTACATC Petition 870260056387, dated 10 / 06 / 2026, page 176 / 926 168 / 305 4. Vectors and host cells

[00123] Vectors comprising one or more polynucleotides encoding one or more of the immunogenic polypeptides described herein, or an expression cassette comprising such polynucleotides, are additionally provided. A vector may be of any type, for example, a recombinant vector, such as an expression vector. Vectors include, but are not limited to, plasmids, cosmids, bacterial artificial chromosomes (BACs) and yeast artificial chromosomes (YACs), and vectors derived from bacteriophages or plant or animal viruses (including human). Vectors may comprise a proposed host cell-recognized origin of replication and, in the case of expression vectors, a promoter and other host cell-recognized regulatory regions. In further embodiments, a vector comprises one or more polynucleotides encoding one or more immunogenic revelation polypeptides functionally linked to a promoter and, optionally, additional regulatory elements.Certain vectors are capable of autonomous replication in a host into which they are introduced (for example, vectors having a bacterial origin of replication can replicate in bacteria). Other vectors can be integrated into a host's genome after introduction into the host and thus are replicated along with the host genome. Vectors include, but are not limited to, those suitable for the recombinant production of the immunogenic polypeptides disclosed herein.

[00124] The term vector, as used in this document, refers to a nucleic acid molecule capable of propagating another nucleic acid to which it is attached. The term includes the vector as a self-replicating nucleic acid structure, as well as the vector incorporated into the genome of a host cell into which it has been introduced. Some vectors are suitable for delivering the nucleic acid or polynucleotide molecule of the present application. Certain vectors are capable of directing the Petition 870260056387, dated 10 / 06 / 2026, page 177 / 926 169 / 305 expression of nucleic acids to which they are operationally linked. Such vectors are referred to in this document as expression vectors.

[00125] The term functionally linked refers to two or more nucleic acid sequences or polypeptide sequence elements that are generally physically linked and are in a functional relationship with each other. For example, in the context of nucleic acid sequence elements, a promoter is functionally linked to a coding sequence if the promoter is capable of initiating or regulating the transcription or expression of a coding sequence, in which case the coding sequence should be understood as being under the control of the promoter.

[00126] The choice of vector depends on the recombinant procedures followed and the host used. The introduction of vectors into host cells can be performed, among others, by transfection with calcium phosphate, DEAE-dextran-mediated transfection, lipofectamine transfection, electroporation, viral infection, or through administration to an individual, as described herein. Vectors may be autonomously replicating or may replicate together with the chromosome into which they have been integrated. In certain embodiments, vectors contain one or more selection markers. The choice of markers may depend on the host cells of choice. These include, but are not limited to, kanamycin, neomycin, puromycin, hygromycin, zeocin, Herpes simplex virus (HSV-TK) thymidine kinase gene, and mouse dihydrofolate reductase (dhfr) gene.Also covered by the disclosure are vectors comprising one or more nucleic acid molecules encoding the immunogenic polypeptides described herein, functionally linked to one or more nucleic acid molecules encoding proteins or peptides that can be used to isolate the immunogenic polypeptides. These proteins or peptides include, but... Petition 870260056387, dated 10 / 06 / 2026, page 178 / 926 170 / 305 are not limited to, glutathione-S-transferase, maltose-binding protein, metal-binding polyhistidine, green fluorescent protein, luciferase and beta-galactosidase.

[00127] In other modalities, the vector used is pcDNA™3.1 + (ThermoFisher, MA).

[00128] In some embodiments, the vector is a viral vector. As appropriate, the viral vector may be a DNA virus or an RNA virus, including a self-replicating RNA virus. Self-replicating RNA viruses include alphaviruses and are described, for example, in Lundstrom, Molecules. (2018) 23(12). pii: E3310 (PMID: 30551668); and Ljungberg, et al., Expert Rev Vaccines. (2015) 14(2):177-94). In several embodiments, the viral vector is a virus selected from the group consisting of adenovirus, adeno-associated virus, arenavirus, alphavirus, self-replicating alphavirus, poxvirus, cytomegalovirus, rhabdovirus, vesicular stomatitis virus, flavivirus, Marabá virus, and vaccinia virus. In some forms, the viral vector is from a selected viral family from the group consisting of: Adenoviridae (e.g., adenovirus, adeno-associated virus), Arenaviridae (e.g., lymphocytic choriomeningitis mamarenavirus, Cali mamarenavirus (also called Pichindé mamarenavirus (PICV)),Poxviridae (e.g., vaccinia virus), Herpesviridae (e.g., cytomegalovirus, herpesvirus, e.g., HSV1), Parvoviridae (e.g., parvovirus H1), Poxviridae (e.g., vaccinia virus, e.g., modified Ankara vaccinia (MVA)), Flaviviridae (e.g., yellow fever virus), Reoviridae (e.g., reovirus), Retroviridae (e.g., lentivirus), Picornaviridae (e.g., Coxsackie virus, Seneca Valley virus, poliovirus), Paramyxoviridae (e.g., measles virus, Newcastle disease virus (NDV)), Rhabdoviridae (e.g., vesiculoviruses, including Marabá vesiculovirus and vesicular stomatitis virus (VSV)), Togaviridae (e.g., alphaviruses, e.g., self-replicating alphavirus; Sindbis virus), Petition 870260056387, dated 10 / 06 / 2026, page 179 / 926 171 / 305 Enteroviridae (e.g., echovirus). Illustrative modified vaccinia viral vectors for use in expressing the present immunogenic polypeptides are described, for example, in document WO 2019 / 134049.

[00129] In some embodiments, the viral expression vector is an arenavirus vector selected from among lymphocytic choriomeningitis mamarenavirus (LCMV)(NCBI:txid11623), Cali mamarenavirus (also called Pichindé mamarenavirus or Pichindé arenavirus) (NCBI:txid2169993), Guanarito virus (GTOV) (NCBI:txid45219), Argentine mamarenavirus (also called Junín virus (JUNV))(NCBI: txid2169991), Lassa virus (LASV)(NCBI:txid11620), Lujo virus (LUJV) (NCBI:txid649188), Machupo virus (MACV)(NCBI:txid11628), Brazilian mamarenavirus (also called Sabiá virus (SABV))(NCBI: txid2169992), and viruses Whitewater Arroyo (WWAV)(NCBI:txid46919). In some embodiments, the viral expression vector is an arenavirus vector selected from lymphocytic choriomeningitis mamarenavirus (LCMV) or Cali mamarenavirus (also called Pichindé mamarenavirus or Pichindé arenavirus (PICV)).Illustrative arenaviral vectors that can be used as delivery and expression vehicles for the immunogenic polypeptides described in the present invention are described, for example, in documents WO 2009 / 083210; WO 2015 / 183895; WO 2016 / 075250; WO 2017 / 198726; and in US patents Nos. 9,943,585 and 10,342,861, which are incorporated herein by reference in their entirety for all purposes.

[00130] In some embodiments, the viral expression vector is an adenoviral vector, for example, of a human adenovirus or a simian adenovirus (e.g., a chimpanzee adenovirus, a gorilla adenovirus, or a rhesus monkey adenovirus). In several embodiments, the adenoviral vector is an adenoviral vector selected from adenovirus serotype 5 (Ad5), adenovirus serotype 26 (Ad26), or serotype 34 of Petition 870260056387, dated 10 / 06 / 2026, pp. 180 / 926 172 / 305 adenovirus (Ad34), adenovirus serotype 35 (Ad35), adenovirus serotype 48 (Ad48), chimpanzee adenovirus (e.g., ChAdOx1, ChAdOx2, ChAd3 (AdC3), ChAd5 (AdC5), ChAd6 (AdC6), ChAd7 (AdC7), ChAd8 (AdC8), ChAd9 (AdC9), ChAd10 (AdC10), ChAd11 (AdC11), ChAd17 (AdC17), ChAd16 (AdC16), ChAd19 (AdC19), ChAd20 (AdC20), ChAd22 (AdC22), ChAd24 (AdC24), ChAdY25, ChAd26 (AdC26), ChAd28 (AdC28), ChAd30 (AdC30), ChAd31 (AdC31), ChAd37 (AdC37), ChAd38 (AdC38), ChAd43 (AdC43), ChAd44 (AdC44), ChAd55 (AdC55), ChAd63 (AdC63), ChAdV63, ChAd68 (AdC68), ChAd73 (AdC73), ChAd82 (AdC82), ChAd83 (AdC83), ChAd143 (AdC143), ChAd144 (AdC144), ChAd145 (AdC145), ChAd147 (AdC147)), gorilla adenovirus (e.g., GC44, GC45, GC46) and rhesus adenovirus (e.g., RhAd51, RhAd52, RhAd53, RhAd54, RhAd55, RhAd56, RhAd57, RhAd58, RhAd59, RhAd60, RhAd61, RhAd62, RhAd63, RhAd64, RhAd65, RhAd66).Illustrative chimpanzee, gorilla, and rhesus adenoviral vectors that can be used as delivery and expression vehicles for the immunogenic polypeptides described herein are described, for example, WO2012 / 172277 (ChAdOx1), WO2017 / 221031 (ChAdOx2), WO2019 / 076880; WO2019 / 076877; Andrabi et al., (2019) Cell Reports 27:2426-2441; Guo, et al., Hum Vaccin Immunother. (2018) 14(7):1679-1685; Abbink, et al., J Virol. (2015) 89(3):1512-22; and Abbink, et al., J Virol. (2018) 92(6). pii: e01924-17.

[00131] In several embodiments, the viral expression vector is incapable of replicating (i.e., it is replication-defective or replication-deficient), has reduced or diminished replication capacity, for example, compared to a wild-type viral vector (i.e., it is attenuated for replication), or is replication-competent. In several embodiments, the viral expression vector is a replication-defective or replication-deficient arenavirus vector that has a bisegmented genome, for example, as Petition 870260056387, dated 10 / 06 / 2026, page 181 / 926 173 / 305 described in documents WO 2009 / 083210 and WO 2017 / 076988. In several embodiments, the viral expression vector is an attenuated arenavirus vector for replication that has a trisegmented genome, for example, as described in documents WO 2016 / 075250, WO 2017 / 076988 and WO 2017 / 198726.

[00132] Host cells comprising one or more polynucleotides encoding one or more of the immunogenic polypeptides or one or more vectors expressing the immunogenic polypeptides, as described herein, are additionally provided. Any of a variety of host cells may be used. In one embodiment, a host cell is a prokaryotic cell, for example, E. coli. In another embodiment, a host cell is a eukaryotic cell, for example, a yeast cell, a plant cell, an insect cell, a mammalian cell, such as a Chinese Hamster Ovary (CHO)-based cell line or CHO-derived cell line (e.g., CHO-S, CHO DG44, ExpiCHO™, CHOZN® ZFN-modified CHO cell line, CHO-K1, CHO-K1a), COS cells, BHK cells, NSO cells, or Bowes melanoma cells.Examples of human host cells include, among others, HeLa, 911, AT1080, A549, and HEK293 (e.g., HEK293F, HEK293H, HEK293T, Expi293™). Furthermore, immunogenic polypeptides can be expressed in yeast cells such as Pichia (see, for example, Powers et al., J Immunol Methods. 251:123-35 (2001)), Hanseula, or Saccharomyces.

[00133] The terms host cell, host cell line, and host cell culture are used interchangeably and refer to cells into which exogenous nucleic acid has been introduced, including the offspring of such cells. Host cells include transformants and transformed cells, which Petition 870260056387, dated 10 / 06 / 2026, page 182 / 926 174 / 305 include the primary transformed cell and its derived progeny without regard to the number of passages. The progeny may not be completely identical in nucleic acid content to a progenitor cell, but may contain mutations. Mutant progeny that has the same biological function or activity as screened or selected in the originally transformed cell is included in this document.

[00134] As appropriate, host cells may be stably or transiently transfected with one or more polynucleotides encoding one or more immunogenic polypeptides, as described herein. As appropriate, host cells may be infected with one or more vectors expressing one or more immunogenic polypeptides, as described herein. In some embodiments, host cells are capable of being infected with and propagating one or more attenuated or replication-competent vectors expressing one or more immunogenic polypeptides, as described herein. Useful illustrative cells for infecting with and / or propagating viral vectors include, without limitation, BHK-21, A549, Vero, and HEK293 (e.g., HEK293E, HEK293F, HEK293H, HEK293T, Expi293™ cells). In certain forms, host cells express the Coxsackie virus and adenovirus receptor (CAR), for example, MDCK, Caco-2, or Calu-3 host cells.In certain forms, polynucleotides integrate into the host cell's genome. 5. Pharmaceutical compositions / immunogenic compositions

[00135] Pharmaceutical compositions or immunogenic compositions are provided comprising one or more of the immunogenic HBV polypeptides as described herein, or a polynucleotide encoding one or more of the immunogenic HBV polypeptides as described herein, or a viral expression vector comprising one or more Petition 870260056387, dated 10 / 06 / 2026, page 183 / 926 175 / 305 of these polynucleotides, and a pharmaceutically acceptable diluent, carrier, or excipient. A pharmaceutically acceptable excipient includes, but is not limited to, any adjuvant, carrier, excipient, fluidifier, sweetening agent, diluent, preservative, colorant / coloring agent, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier that has been approved by the United States Food and Drug Administration as acceptable for use in humans or domestic animals.

[00136] Generally, the pharmaceutical compositions described herein are immunogenic. In certain embodiments, the pharmaceutical composition comprises a therapeutically effective amount of one or more (e.g., two or more, three or more) immunogenic HBV polypeptides, or one or more (e.g., two or more, three or more) polynucleotides encoding one or more (e.g., two or more, three or more) of the immunogenic HBV polypeptides, or one or more (e.g., two or more, three or more) viral expression vectors containing one or more (e.g., two or more, three or more) of the polynucleotides encoding one or more of the immunogenic HBV polypeptides.

[00137] Various pharmaceutically acceptable diluents, carriers and excipients, and techniques for the preparation and use of pharmaceutical compositions will be known to those skilled in the art in the light of the present disclosure.Illustrative pharmaceutical compositions and pharmaceutically acceptable diluents, vehicles, and excipients are also described, for example, in Loyd V. Allen Jr. (Editor), Remington: The Science and Practice of Pharmacy, 22nd Edition, 2012, Pharmaceutical Press; Brunton, Knollman and Hilal-Dandan, Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition, 2017, McGraw-Hill Education / Medical; McNally and Hastedt (Editors), Protein Formulation and Delivery, 2nd Edition, 2007, CRC Press; Banga, Therapeutic Peptides and Proteins. Petition 870260056387, dated 10 / 06 / 2026, page 184 / 926 176 / 305 Formulation, Processing, and Delivery Systems, 3aEdição, 2015, CRC Press; Lars Hovgaard, Frokjaer e van de Weert (Editores), Pharmaceutical Formulation Development of Peptides and Proteins, 2a. Edição, 2012, CRC Press; Carpenter e Manning (Editores), Rational Design of Stable Protein Formulations: Theory and Practice, 2002, Springer (Pharmaceutical Biotechnology (Livro 13)); Meyer (Editor), Therapeutic Protein Drug Products: Practical Approaches to Formulation in the Laboratory, Manufacturing, and the Clinic, 2012, Woodhead Publishing.

[00138] In certain embodiments, polynucleotides or vectors are formulated into lipid nanoparticles. For example, in some embodiments where immunogenic HBV polypeptides are expressed from self-replicating or self-amplifying RNA molecules, the self-replicating RNA or self-amplifying RNA can be formulated into lipid nanoparticles (LNPs). As used in this document, the term lipid nanoparticle refers to one or more spherical nanoparticles with an average diameter between about 10 and about 1,000 nanometers comprising a solid lipid core matrix that can solubilize lipophilic molecules.In certain embodiments, the lipid core is stabilized by surfactants (e.g., emulsifiers) and may comprise one or more of the following: triglycerides (e.g., tristearin), diglycerides (e.g., glycerol behenate), monoglycerides (e.g., glycerol monostearate), fatty acids (e.g., stearic acid), steroids (e.g., cholesterol), and waxes (e.g., cetyl palmitate), including combinations thereof. Lipid nanoparticles are described, for example, in Petrilli et al., Curr Pharm Biotechnol. 15:847-55, 2014; and in US patents no. 6,217,912; 6,881,421; 7,402,573; 7,404,969; 7,550,441; 7,727,969; 8,003,621; 8,691,750; 8,871,509; 9,017,726; 9,173,853; 9,220,779; 9,227,917; and 9,278,130, each of which is incorporated herein into Petition 870260056387, dated 10 / 06 / 2026, page 185 / 926 177 / 305 reference title in its entirety. In one embodiment, a self-replicating or self-amplifying RNA molecule encoding one or more of the immunogenic HBV polypeptides described herein is formulated or condensed into polyethyleneimine (PEI)-polyplex delivery vehicles, for example, as described in Démoulins, et al., Nanomedicine. (2016) Apr;12(3):711-722 and Démoulins, et al., J Control Release. (2017) Nov 28;266:256-271, which may be nanoparticulate.

[00139] In embodiments where immunogenic HBV polypeptides are expressed from a viral expression vector, the viral expression vector may be formulated for a desired route of administration, for example, as a pharmaceutically acceptable isotonic aqueous solution or suspension suitable for intravenous, intramuscular, subcutaneous, or intradermal administration. In some embodiments, the viral expression vector may be formulated for mucosal release, for example, buccal, intranasal, intravaginal, or intrarectal.Illustrative formulations for viral expression vectors that can be used in the pharmaceutical compositions and methods described herein are described, for example, in Manfredsson and Benskey, Editors, Viral Vectors for Gene Therapy: Methods and Protocols (Methods in Molecular Biology), 2019, Book 1937 in Methods in Molecular Biology Series, Humana Press; WO 2017 / 013169 (formulation of adenoviral vectors in an aqueous mixture or freeze-dried composition in the presence of amorphous sugar and low salt concentration); and Kumru, et al., J Pharm Sci. (2018) Nov;107(11):2764-2774 (aqueous formulations buffered in Tris and containing proline, lactose, and mannitol as stabilizing additives). The formulation of arenaviral vectors is described, for example, in documents WO 2009 / 083210; WO 2016075250 and WO 2017 / 198726. In certain modalities, viral expression vectors are delivered by microneedle-mediated delivery, for example, as described in Zaric, et al.,. Petition 870260056387, dated 10 / 06 / 2026, p. 186 / 926 178 / 305 Opin Drug Deliv Specialist. (2017) Oct; 14(10):1177-1187.

[00140] In some embodiments, each carrier, diluent, or excipient is acceptable in the sense that it is compatible with the other ingredients of the pharmaceutical composition and not harmful to the individual. Frequently, the pharmaceutically acceptable vehicle is a pH-buffered aqueous solution. Some examples of materials that may serve as pharmaceutically acceptable vehicles, diluents, or excipients include: water; buffers, for example, a buffer having a pKa in the range of about 6.0 to about 8.0, for example, a physiologically acceptable buffer, for example, selected from phosphate, carbonate, bicarbonate, citrate, maleate, glycine-glycine, HEPES, HEPPSO, HEPPS, imidazole, BICINE, TRICINE, Tris, and BIS-Tris; sugars, such as lactose, trehalose, glucose, and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethylcellulose, ethyl cellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc;Excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol; polyols such as glycerin, sorbitol, mannitol, and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline solution; Hank's solution, Ringer's solution; ethyl alcohol; phosphate buffer solutions; amino acids (e.g., charged amino acids, including but not limited to aspartate, asparagine, glutamate, glutamine, histidine, arginine, lysine);and other compatible non-toxic substances used in pharmaceutical formulations. Humectants, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening agents, and flavorings; Petition 870260056387, dated 10 / 06 / 2026, page 187 / 926 179 / 305 artificial colors and fragrances, preservatives and antioxidants may also be present in the compositions.

[00141] In a particular formulation, an arenavirus vector (e.g., an LCMV or Pichindé mamarenavirus (PICV) vector) described herein is formulated in an isotonic aqueous solution comprising a biologically compatible buffer with a pKa in the range of about 6.0 to about 8.0 (e.g., HEPES and NaCl), at a neutral or near-neutral pH and a nonionic surfactant (e.g., PLURONIC® F68 (also called poloxamer 188)). In a specific formulation, an arenavirus vector (e.g., an LCMV or Pichindé mamarenavirus vector) described herein is formulated in an isotonic aqueous solution comprising HEPES buffer at pH 7.4, NaCl, and PLURONIC® F68 (also called poloxamer 188). Schleiss, et al. (Clin Vaccine Immunol. January 5, 2017;24(1):e00300-16) describes an LCMV formulation of LCMV vectors in a diluent of 25 mM HEPES, 150 mM NaCl, 0.01% PLURONIC® F68; pH 7.4), which can be used to formulate the arenaviral vectors described herein.A final concentration of 10% sorbitol was added before freezing below -60 °C.

[00142] The formulation and delivery methods of pharmaceutical compositions will generally be adapted according to the site and disease to be treated. Exemplary formulations include, but are not limited to, those suitable for parenteral administration, for example intravenous, intra-arterial, intramuscular or subcutaneous administration, including formulations encapsulated in micelles, liposomes or drug-release capsules (active agents incorporated within a biocompatible coating designed for slow release); ingestible formulations; formulations for topical use, such as creams, ointments and gels; and other formulations such as inhalants, aerosols and sprays. In some embodiments, the pharmaceutical compositions Petition 870260056387, dated 10 / 06 / 2026, pp. 188 / 926 180 / 305 cas are formulated for parenteral administration, for example intravenous, subcutaneous or oral. In some embodiments, the pharmaceutical compositions are formulated for mucosal administration, for example, buccal, intranasal, intrathecal and / or intravaginal.

[00143] In certain embodiments, the pharmaceutical compositions are sterile. In certain embodiments, the pharmaceutical composition has a pH in the range of 4.5 to 8.5, 4.5 to 6.5, 6.5 to 8.5, 6.0 to 8.0, 6.5 to 8.5 or a pH of about 5.0, about 5.5, about 6.0, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.5, about 8.0 or about 8.5. In one embodiment, the pharmaceutical composition has an osmolarity in the range of 240 to 260 or 250 to 330 mOsmol / L. In certain formulations, the pharmaceutical composition is isotonic or nearly isotonic.

[00144] In some embodiments, the pharmaceutical compositions are liquid or solid. In some embodiments, the pharmaceutical composition comprises an aqueous solution or suspension. In some embodiments, the pharmaceutical composition is lyophilized or is a frozen liquid.

[00145] In some embodiments, the pharmaceutical composition further comprises one or more additional therapeutic agents, for example, a second therapeutic agent, or second and third therapeutic agents, for use in combination therapies, as described herein.

[00146] In certain embodiments, the pharmaceutical composition further comprises an adjuvant. Illustrative adjuvants that may be co-formulated or co-administered with the immunogenic HBV polypeptides described herein, polynucleotides encoding such immunogenic HBV polypeptides, and vectors expressing such immunogenic HBV polypeptides include, but are not limited to, cytokines, chemokines, molecules Petition 870260056387, dated 10 / 06 / 2026, p. 189 / 926 181 / 305 immunological co-stimulatory agents, Toll-like receptor agonists or inhibitors of immunosuppressive pathways, as described here, and in Li, et al., Curr Issues Mol Biol. (2017) 22:17-40.Other adjuvants that may be co-formulated or co-administered with the immunogenic HBV polypeptides described herein, polynucleotides encoding such immunogenic HBV polypeptides, and vectors expressing such immunogenic HBV polypeptides include, but are not limited to, mineral salts (e.g., aluminum salts (e.g., alum), calcium phosphate, Freund's incomplete adjuvant), lipid particles (e.g., MF59, chelates, virus-like particles), microparticles (e.g., virosomes, polylactic acid (PLA), poly(lactide-coglycolide) (PLG)), immunoenhancers (e.g., dsRNA:Poly(I:C), poly-IC:LC, monophosphoryl lipid A (MPL), lPS, flagellin, imidazoquinolines: imiquimod (R837), resiquimod (R848), CpG oligodeoxynucleotides (ODN), muramyl dipeptide (MDP), saponins (QS-21) and mucosal adjuvants (e.g., cholera toxin (CT), heat-labile enterotoxins (LTK3 and LTR72), chitosan).The adjuvants that can be co-formulated or co-administered with the immunogenic HBV polypeptides described herein, polynucleotides encoding such immunogenic HBV polypeptides, and vectors expressing such immunogenic HBV polypeptides are summarized in Apostolic, et al., J Immunol Res. (2016) 2016:1459394.

[00147] In some embodiments, the pharmaceutical compositions or immunogenic compositions comprise mixtures of two or more immunogenic HBV polypeptides, two or more polynucleotides encoding such immunogenic HBV polypeptides, or two or more vectors expressing such immunogenic HBV polypeptides. In some embodiments, the pharmaceutical composition comprises two or more immunogenic HBV polypeptides, two or more polynucleotides encoding such immunogenic HBV polypeptides, or two or more vectors expressing such HBV polypeptides. Petition 870260056387, dated 10 / 06 / 2026, pp. 190 / 926 182 / 305 immunogenic.

[00148] In several embodiments, the immunogenic composition comprises one or more coding polynucleotides, or one or more vectors capable of expressing, two immunogenic polypeptides, wherein the immunogenic polypeptides comprise: (a) a mutant HBV polymerase polypeptide comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 5 to 14, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 5 to 14; and (b) an HBV core-sAg fusion protein comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 38 to 41, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 38 to 41.

[00149] In several embodiments, the immunogenic composition comprises one or more coding polynucleotides, or one or more vectors capable of expressing, two immunogenic polypeptides, wherein the immunogenic polypeptides comprise: (a) a mutant HBV polymerase polypeptide comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 13 to 14, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 13 to 14; and (b) an HBV core-sAg fusion protein comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 38 to 41, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 38 to 41.

[00150] In several modalities, the immunogenic composition compre Petition 870260056387, dated 10 / 06 / 2026, p. 191 / 926 183 / 305 contains one or more polynucleotides encoding, or one or more vectors capable of expressing, two immunogenic polypeptides, wherein the immunogenic polypeptides comprise: (a) a mutant HBV polymerase polypeptide comprising or consisting of an amino acid sequence of SEQ ID NO: 13, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 13; and (b) an HBV core-sAg fusion protein comprising or consisting of an amino acid sequence from SEQ ID NO: 41, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 41.

[00151] Regarding the core-sAg fusion polypeptide in the immunogenic composition, in some embodiments, the core polypeptide comprises a serine (S) residue at the amino acid position corresponding to position 12, and an asparagine (N) residue at the amino acid position corresponding to position 67, with the position numbers referring to SEQ ID NO:65 or SEQ ID NO:66. In some embodiments, the sAg polypeptide comprises an isoleucine (I) residue at the amino acid position corresponding to position 68, with the position numbers referring to SEQ ID NO:3 or SEQ ID NO:4.In some embodiments, the sAg polypeptide comprises one or more of the following: a serine (S) residue at the amino acid position corresponding to position 53, an isoleucine (I) residue at the amino acid position corresponding to position 68, a threonine (T) residue at the amino acid position corresponding to position 125, a proline (P) residue at the amino acid position corresponding to position 127, a phenylalanine (F) residue at the amino acid position corresponding to position 161, a tyrosine (Y) residue at the amino acid position corresponding to position 200, a serine (S) residue at the... Petition 870260056387, dated 10 / 06 / 2026, pp. 192 / 926 184 / 305 amino acid position corresponding to position 210, and a leucine (L) residue at the amino acid position corresponding to position 213, wherein the position numbers are reference to SEQ ID NO:3 or SEQ ID NO:4. In some embodiments, the sAg core fusion polypeptide comprises one or more of the following: a serine (S) residue at the amino acid position corresponding to position 12, an asparagine (N) residue at the amino acid position corresponding to position 67, a valine (V) residue at the amino acid position corresponding to position 74, a phenylalanine (F) residue at the amino acid position corresponding to position 97, a threonine (T) residue at the amino acid position corresponding to position 249, a threonine (T) residue at the amino acid position corresponding to position 250, a serine (S) residue at the amino acid position corresponding to position 317, a serine (S) residue at the amino acid position corresponding to position 318,an arginine residue (R) at the amino acid position corresponding to position 326, a tyrosine residue (Y) at the amino acid position corresponding to position 338, a glycine residue (G) at the amino acid position corresponding to position 363, and an alanine residue (A) at the amino acid position corresponding to position 372, where the position numbers are with reference to SEQ ID NO:41.

[00152] In some embodiments, the immunogenic composition comprises a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of any of the SEQ ID NOs: 27 to 32 and 89 to 94, for example, SEQ ID NOs: 29, 89, 90 or 92, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 27 to 32 and 89 to 94, for For example, SEQ IDs: 29, 89, 90 and 92; and (b) the second viral expression vector comprises Petition 870260056387, dated 10 / 06 / 2026, p. 193 / 926 185 / 305 is a polynucleotide comprising or consisting of a nucleic acid sequence of any of the SEQ ID Nos: 33 to 37 or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID Nos: 33 to 37.

[00153] In some embodiments, the immunogenic composition comprises a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of SEQ ID NO: 29 or 90, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NOs: 29, 89, 90 or 92; and (b) the second viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 37 or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 37.

[00154] In some embodiments, the immunogenic composition comprises a first LCMV arenavirus expression vector and a second LCMV arenavirus expression vector, wherein: (a) the first LCMV arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 29, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 29; and (b) the second LCMV arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 37 or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, Petition 870260056387, dated 10 / 06 / 2026, pp. 194 / 926 186 / 305 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 37.

[00155] In some embodiments, the immunogenic composition comprises a first Pichindé arenavirus expression vector and a second Pichindé arenavirus expression vector, wherein: (a) the first Pichindé arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of SEQ ID NO: 90, or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 90; and (b) the second Pichindé arenavirus expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 37 or a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NO: 37.

[00156] As appropriate or desired, the mutant HBV polymerase polypeptide and the HBV-sAg core fusion protein may be provided in the immunogenic composition in a ratio in the range of 1:10 to 10:1, for example, in the range of 1:9 to 9:1, 1:8 to 8:1, 1:7 to 7:1, 1:6 to 6:1, 1:5 to 5:1, 1:4 to 4:1, 1:3 to 3:1, 1:2 to 2:1 or 1:1. In various embodiments, the ratios may be measured in plaque-forming units (PFU), focus-forming units (FFU), infectious units (IU) or viral particles (vp).

[00157] In various forms, one or more polynucleotides are self-replicating DNA, cDNA, mRNA, or RNA.

[00158] In some embodiments, the immunogenic composition comprises a first viral expression vector and a second viral expression vector, wherein: (a) the first viral expression vector comprises a polynucleotide encoding a polymerase polypeptide Petition 870260056387, dated 10 / 06 / 2026, pp. 195 / 926 (a) the first viral expression vector comprises a truncated HBV 187 / 305 or a mutant HBV polymerase deletion polypeptide, as described herein; and (b) the second viral expression vector comprises a polynucleotide encoding the nucleoside-sAg fusion protein, as described herein. As appropriate or desired, the first viral expression vector and the second viral expression vector may be provided in a ratio in the range of 1:10 to 10:1, for example, in the range of 1:9 to 9:1, 1:8 to 8:1, 1:7 to 7:1, 1:6 to 6:1, 1:5 to 5:1, 1:4 to 4:1, 1:3 to 3:1, 1:2 to 2:1 or 1:1.

[00159] In some embodiments, the immunogenic composition comprises in the range of about 103 to about 1012 focus-forming units (FFU) or plaque-forming units (PFU) or viral infectious units (UI) or viral particles (vp), for example, from about 104 to about 107 viral FFU or PFU, for example, from about 103 to about 104, 105, 106, 107, 108, 109, 1010, 1011 or 1012 viral FFU or PFU or IU or vp per milliliter, of each of the first viral expression vector and the second viral expression vector.

[00160] In several embodiments, the first viral expression vector and the second viral expression vector in the immunogenic composition are independently of a taxonomic family selected from Adenoviridae, Arenaviridae, Herpesviridae (e.g., cytomegalovirus), Poxviridae (e.g., vaccinia virus, e.g., modified Ankara vaccinia (MVA)), Flaviviridae (e.g., yellow fever virus), Rhabdoviridae (e.g., vesiculovirus, e.g., Marabá vesiculovirus), Togaviridae (e.g., alphaviruses). In several embodiments, the first viral expression vector and the second viral expression vector may be from the same taxonomic family or from different taxonomic families. For example, in some embodiments, both the first viral expression vector and the second viral expression vector in the immunogenic composition are from Adenoviridae, Arenaviridae, or Poxviridae (e.g., vaccinia virus, e.g., Petition 870260056387, dated 10 / 06 / 2026, p. 196 / 926 188 / 305 vaccinia Ankara modified (MVA).

[00161] In some embodiments, the first viral expression vector and the second viral expression vector in the immunogenic composition are Arenaviridae. In some embodiments, the first viral expression vector and the second viral expression vector are an arenavirus vector selected from lymphocytic choriomeningitis mamarenavirus (LCMV), Cali mamarenavirus (also called Pichindé mamarenavirus or Pichindé arenavirus (PICV)), Guanarito virus (GTOV), Junín virus (JUNV), Lassa virus (LASV), Lujo virus (LUJV), Machupo virus (MACV), Sabiá virus (SABV), and Whitewater Arroyo virus (WWAV). In some embodiments, the first viral expression vector and the second viral expression vector are an arenavirus vector selected from lymphocytic choriomeningitis mamarenavirus (LCMV) or Cali mamarenavirus (also called Pichindé mamarenavirus or Pichindé arenavirus (PICV)).

[00162] In several embodiments, the first viral expression vector and the second viral expression vector in the immunogenic composition are defective for replication or deficient for replication. In some embodiments, the first viral expression vector and the second viral expression vector in the immunogenic composition are attenuated for replication. 6. Treatment methods

[00163] Methods are additionally provided for eliciting an immune response to the human hepatitis B virus (HBV) in an individual who needs them. Methods for treating or preventing the human hepatitis B virus (HBV) in an individual who needs them are also provided. Methods for inhibiting HBV replication in an infected individual are also provided. Methods for reducing the viral load associated with HBV infection are additionally provided. In various embodiments, the methods Petition 870260056387, dated 10 / 06 / 2026, page 197 / 926 189 / 305 comprise administering to the individual an effective amount of an immunogenic composition, as described herein. In various embodiments, the subject or individual is a human being, a marmot, a Peking duck, a mouse, or a non-human primate (e.g., a chimpanzee).

[00164] Treatment, to treat, or that which treats, as used herein, refers to an approach to obtain beneficial or desired results. For the purposes of this disclosure, beneficial or desired results include, but are not limited to, relief of a symptom and / or reduction in the extent of a symptom, delay in the progression and / or prevention of a worsening of a symptom associated with a disease or condition.Treatment or what to treat may include one or more of the following: a) inhibition of the disease or condition (e.g., reduction of one or more symptoms resulting from the disease or condition and / or reduction in the extent of the disease or condition); b) delay or interruption of the development of one or more symptoms associated with the disease or condition (e.g., stabilization of the disease or condition, delay in the worsening or progression of the disease or condition); and c) relief of the disease or condition, for example, causing regression of clinical symptoms, improving disease status, delaying disease progression, increasing quality of life and / or prolonging survival.

[00165] Delay, as used herein, refers to the development of means of treating a disease or condition to postpone, impede, reduce, slow down, stabilize, and / or delay the development of the disease or condition. This delay may be of varying lengths of time, depending on the history of the disease and / or the individual being treated. As is evident to one skilled in the art, a sufficient or significant delay may, in fact, encompass prevention, such that the individual does not develop the disease or condition.

[00166] To prevent or prevention or that which prevents as used Petition 870260056387, dated 10 / 06 / 2026, pp. 198 / 926 190 / 305 here refers to a regimen that protects against the onset of the disease or disorder, so that the clinical symptoms of the disease do not develop. Thus, prevention refers to administering a therapy (e.g., administering a therapeutic substance) to an individual before signs of the disease are detectable in the individual (e.g., administering a therapeutic substance to an individual in the absence of a detectable infectious agent (e.g., virus) in the individual). The individual may be an individual at risk of developing the disease or disorder, such as an individual who has one or more risk factors known to be associated with the development or onset of the disease or disorder. Thus, in certain modalities, the term preventing HBV infection refers to administering an anti-HBV therapeutic substance to an individual who does not have a detectable HBV infection.It is understood that an individual eligible for preventive anti-HBV therapy may be an individual at risk of contracting the HBV virus. It is also understood that prevention does not require a 100% success rate. In some cases, prevention may be understood as a reduction in the risk of infection, but not a complete elimination of the occurrence of an infection.

[00167] Therapeutically effective amount or effective amount, as used herein, refers to an amount that is effective in eliciting the desired biological or clinical response, including the amount of an immunogenic composition that, when administered to an individual for the treatment of a disease, is sufficient to effect such treatment for the disease. The effective amount will vary depending on the immunogenic composition, the disease and its severity, ...

Claims

1. Truncated hepatitis B virus (HBV) polymerase polypeptide, characterized by comprising an inactivated reverse transcriptase domain and an inactivated RNase H, wherein the polypeptide is not more than 600 amino acids in length and does not comprise the entire terminal protein (TP) domain and does not comprise all or part of the spacer domain, wherein the polypeptide comprises an amino acid sequence from any of the SEQ ID NOs: 13-14.

2. Fusion protein, characterized by comprising, in sequential order from the N-terminal to the C-terminal, an HBV core polypeptide and a small HBV surface antigen (sAg) polypeptide, wherein the fusion protein is no more than 450 amino acids in length, does not comprise an HBV pre-S1 polypeptide and / or an HBV pre-S2 polypeptide, and wherein the core polypeptide is of an HBV genotype D and the sAg polypeptide is of an HBV genotype D, wherein the fusion protein comprises or consists of an amino acid sequence of any of the SEQ ID NOs: 40-41, or an amino acid sequence that is at least 97%, 98% or 99% identical in total length to any of the SEQ ID NOs: 40-41.

3. Arenavirus vector, characterized by comprising a polynucleotide encoding an HBV nucleoside-sAg fusion polypeptide comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 40 to 41, or an amino acid sequence that is at least 97%, 98% or 99% identical in total length to any of the SEQ ID NOs: 40 to 41, and wherein the sAg polypeptide is no more than 450 amino acids long and does not comprise an HBV pre-S1 polypeptide and / or an HBV pre-S2 polypeptide, wherein the polynucleotide comprises or consists of a nucleic acid sequence of any of the Petition 870260056387, dated 10 / 06 / 2026, p. 315 / 926 2 / 8 of the SEQ ID NOS: 35 to 37, or a nucleic acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical in total length to any of the SEQ ID NOS: 35 to 37.

4. Arenavirus vector, characterized by comprising a polynucleotide encoding an HBV nucleoside-sAg fusion polypeptide comprising or consisting of an amino acid sequence from SEQ ID NO: 41, or an amino acid sequence that is at least 97%, 98%, or 99% identical to the total length of SEQ ID NO: 41, and wherein the polypeptide does not comprise an HBV pre-S1 polypeptide and / or an HBV pre-S2 polypeptide, wherein the polynucleotide comprises or consists of a nucleic acid sequence from SEQ ID NO: 37, or a nucleic acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the total length of SEQ ID NO:

37.

5. Arenavirus vector, according to claim 3, characterized by having a bisegmented genome and further comprising a polynucleotide encoding a truncated HBV polymerase comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 13 to 14, and wherein the truncated HBV polymerase is no more than 600 amino acids in length and does not comprise the entire HBV terminal protein (TP) domain and does not comprise all or part of an HBV polymerase spacer domain, wherein the polynucleotide comprises or consists of a nucleic acid sequence of any of the SEQ ID NOs: 29 and 89 to 94, or is at least 99% identical in total length to any of the SEQ ID NOs: 29 and 89 to 94.

6. Arenavirus vector, according to claim 5, Petition 870260056387, dated 10 / 06 / 2026, p. 316 / 926 3 / 8, characterized in that the arenavirus vector is a lymphocytic choriomeningitis (LCMV) mamarenavirus vector and the polynucleotide comprises or consists of the nucleic acid sequence of SEQ ID NO: 29, or is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the total sequence length of DEQ ID NO:

29.

7. Arenavirus vector, according to claim 5, characterized in that the arenavirus vector is a Pichindé mamarenavirus vector (PICV) and polynucleotides comprise or consist of the nucleic acid sequence of SEQ ID NO: 90, or are at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the total sequence length of DEQ ID NO:

90.

8. Arenavirus vector, characterized by comprising a polynucleotide encoding a truncated HBV polymerase comprising or consisting of an amino acid sequence of any of the SEQ ID NOs: 13 to 14, and wherein the truncated HBV polymerase is no more than 600 amino acids in length, does not comprise the entire HBV terminal protein (TP) domain and does not comprise all or part of an HBV polymerase spacer domain, wherein the polynucleotide comprises or consists of a nucleic acid sequence of any of the SEQ ID NOs: 29 and 89 to 94, or is at least 99% identical in total length to any of the SEQ ID NOs: 29 and 89 to 94.

9. Arenavirus vector, according to claim 8, characterized in that the arenavirus vector is a lymphocytic choriomeningitis (LCMV) mamarenavirus vector and the polynucleotide comprises or consists of the nucleic acid sequence of SEQ ID NO: 29, or is at least 99% identical to the total sequence length of DEQ ID NO:

29. Petition 870260056387, dated 10 / 06 / 2026, p. 317 / 926 4 / 8 10. Arenavirus vector, according to claim 8, characterized in that the arenavirus vector is a Pichindé mamarenavirus (PICV) vector and polynucleotides comprise or consist of the nucleic acid sequence of SEQ ID NO: 90, or is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the total sequence length of DEQ ID NO:

90.

11. Arenavirus vector, according to claim 3 or 4, characterized by being defective for replication, deficient for replication, or incompetent for replication.

12. Isolated host cell, characterized by comprising one or more vectors as defined in any one of claims 3 to 11.

13. Kit, characterized in that it comprises one or more unit doses of one or more vectors as defined in any of claims 3 to 11.

14. Immunogenic composition, characterized by comprising a first viral expression vector and a second viral expression vector, wherein the first viral expression vector comprises a polynucleotide encoding a mutant HBV polymerase polypeptide, wherein the polypeptide is no more than 600 amino acids in length, does not comprise the entire terminal protein (TP) domain and does not comprise all or part of the spacer domain, wherein the polypeptide comprises or consists of an amino acid sequence of any of the SEQ ID NOS: 13 to 14; and the second viral expression vector comprises a polynucleotide encoding the core-sAg fusion protein comprising, in sequential order from N-terminus to C-terminus, a core HBV polypeptide and a surface antigen polypeptide. Petition 870260056387, dated 10 / 06 / 2026, p.318 / 926 5 / 8 small (sAg) HBV strain, wherein the fusion protein is no more than 450 amino acids in length, and wherein the core polypeptide is of an HBV genotype D and the sAg polypeptide is of an HBV genotype D, wherein the fusion protein comprises or consists of an amino acid sequence of any of the SEQ ID NOs: 40-41, or an amino acid sequence that is at least 97%, 98%, or 99% identical in total length to any of the SEQ ID NOs: 40-41.

15. Immunogenic composition, according to claim 14, characterized by comprising a first viral expression vector and a second viral expression vector, wherein the first viral expression vector comprises a polynucleotide encoding a mutant HBV polymerase polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 13; and the second viral expression vector comprises a polynucleotide encoding the nucleo-sAg fusion protein comprising or consisting of the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence that is at least 97%, 98% or 99% identical in length to SEQ ID NO:

41.

16. Immunogenic composition, according to claim 14, characterized by comprising a first viral expression vector and a second viral expression vector, wherein: a) the first viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of any of the SEQ ID NOs: 29, 32 and 89 to 94, or a nucleic acid sequence that is at least 99% identical in total length to any of the SEQ ID NOs: 29, 32 and 89 to 94; b) the second viral expression vector comprises a polynucleotide. Petition 870260056387, dated 10 / 06 / 2026, p. 319 / 926 6 / 8 nucleotide comprising or consisting of a nucleic acid sequence of any of the SEQ ID NOs: 33 to 37 or a nucleic acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical in total length to any of the SEQ ID NOs: 33 to 37.

17. Immunogenic composition, according to claim 16, characterized by comprising a first viral expression vector and a second viral expression vector, wherein: a) the first viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence of any of the SEQ ID NOs: 29, 89, 90 or 92, or a nucleic acid sequence that is at least 99% identical in total length to any of the SEQ ID NOs: 29, 89, 90 or 92; (b) the second viral expression vector comprises a polynucleotide comprising or consisting of a nucleic acid sequence from SEQ ID NO: 37 or a nucleic acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the total length of SEQ ID NO:

37.

18. Immunogenic composition, according to claim 14, characterized in that the first viral expression vector and the second viral expression vector are independently of a taxonomic family selected from Adenoviridae, Arenaviridae, Herpesviridae, Poxviridae, Flaviviridae, Rhabdoviridae and Togaviridae.

19. Immunogenic composition, according to claim 14, characterized in that the first viral expression vector and the second viral expression vector are from the same taxonomic family.

20. Immunogenic composition, according to claim 19, characterized in that the first viral expression vector and the second viral expression vector are from Arenaviridae.

21. Immunogenic composition, according to claim 19, characterized in that the first viral expression vector and the second viral expression vector are independently selected arenavirus vectors from lymphocytic choriomeningitis mamarenavirus (LCMV), Pichindé mamarenavirus (PICV), Guanarito virus (GTOV), Junín virus (JUNV), Lassa virus (LASV), Lujo virus (LUJV), Machupo virus (MACV), Sabiá virus (SABV) and Whitewater Arroyo virus (WWAV).

22. Immunogenic composition, according to claim 19, characterized in that the first viral expression vector and the second viral expression vector are from an arenavirus vector selected from lymphocytic choriomeningitis mamarenavirus (LCMV) or Pichindé mamarenavirus (PICV).

23. Immunogenic composition, according to claim 21, characterized in that the first viral expression vector and the second viral expression vector are defective for replication or deficient for replication.

24. Immunogenic composition, according to claim 19, characterized in that the first viral expression vector and the second viral expression vector have attenuated replication.

25. Immunogenic composition, according to claim 14, characterized in that the first viral expression vector and the second viral expression vector are from different taxonomic families.

26. Immunogenic composition, according to claim 14, characterized in that the first viral expression vector and the second viral expression vector are provided in a ratio in the range of 1:10 to 10:

1.

27. Immunogenic composition, according to claim 14, characterized by comprising in the range of about 103 to about 1012 viral focus-forming units (VFU) or plaque-forming units (PFU) or infectious units (IU) or viral particles (VP) per milliliter of each of the first viral expression vector and second expression vector.

28. Immunogenic composition, according to claim 14, characterized by further comprising one or more adjuvants, a detergent, a micelle-forming agent and an oil.

29. Immunogenic composition, according to claim 14, characterized by being formulated for administration by a route selected from the group consisting of intravenous, intramuscular, intradermal, subcutaneous and mucosal routes.

30. Immunogenic composition, according to claim 14, characterized by being formulated as a liquid.

31. Immunogenic composition, according to claim 14, characterized in that the composition is lyophilized.

32. Kit, characterized by comprising one or more unit doses of the immunogenic compositions, as defined in claim 14.

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