Respiratory syncytial virus mutants, fusion peptides, particles, nucleic acids, pharmaceutical compositions and methods of use

Abstract

Disclosed herein are compositions and methods for controlling respiratory syncytial virus (RSV) infection. In certain embodiments, vaccines and pharmaceutical compositions comprise or encode RSV G proteins comprising the mutations or fusion protein arrangements disclosed herein. In certain embodiments, viral particles / virus-like particles, nucleic acids, vectors, or attenuated RSV vaccines are used in the methods reported herein.

Description

Cross Reference to Related Applications

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 525,447, filed July 7, 2023. The entire contents of the aforementioned application are hereby incorporated by reference in their entirety for all purposes.

[0002] Material submitted electronically via EFS-Web as an XML file

[0003] The Sequence Listing associated with this application is provided in XML format and is hereby incorporated by reference in its entirety. The name of the file containing the Sequence Listing is 22148PCT.xml. The XML file is 43 KB, created on July 2, 2024, and is being submitted electronically via the USPTO Patent Electronic Drawings System. BACKGROUND

[0004] Human respiratory syncytial virus (RSV) causes acute lower respiratory tract infections. It is the leading cause of hospitalization in preterm and newborn infants. RSV infection also poses a threat to the elderly and immunocompromised. Palivizumab, a humanized chimeric antibody that binds to RSV fusion protein (RSV F), is clinically approved for the prevention of severe lower respiratory tract disease caused by RSV in certain high-risk infants. Palivizumab has limited efficacy and can sometimes cause allergic reactions. Thus, there is a need to identify additional RSV therapies.

[0005] Vaccines are typically inactivated or attenuated versions of live strains. Kim et al. reported that administration of a formalin-inactivated RSV vaccine was not ideal. Am J Epidemiol 89, 422-434 (1969). Attenuated RSV vaccine candidates face significant safety hurdles, and developing a live attenuated vaccine (LAV) strain of RSV for children that is fully attenuated and immunogenic has been difficult to achieve. See Collins et al. Progress in understanding and controlling respiratory syncytial virus: still crazy after all these years. Virus Res, 2011, 162, 80-99.

[0006] Quan et al. reported virus-like particles (VLPs) composed of an influenza virus matrix (M1) protein core and RSV-F or RSV-G on the surface. JID, 2011, 204:987-95.

[0007] Hotard et al. reported residues in the human RSV fusion protein that regulate fusion activity and pathogenesis. J Virol, 2015, 89:512-522.

[0008] Rostad et al. reported that a recombinant respiratory syncytial virus candidate vaccine attenuated by low-fusion F protein had immunogenicity and protective effect against challenge in cotton mice. J Virol, 2016, 90(16):7508-7518.

[0009] Ha et al. reported an RSV platform using G, F, or G+F protein VLPs. Viruses, 2020, 12(9): 906.

[0010] Brakel et al. reported that codon optimization of the respiratory syncytial virus (RSV) G protein expressed in a vesicular stomatitis virus (VSV) vector improved the immune response in a rat model. Virology, 2022, 575, 101-110.

[0011] See also U.S. Patent Nos. 10,626,378, 11,235,050, US 2019 / 0292228, WO 2014 / 152534, WO 2015 / 013551 and WO 2017 / 075125.

[0012] The references cited in this article are not an endorsement of existing technology. Overview

[0013] This disclosure relates to compositions and methods for controlling respiratory syncytial virus (RSV) infection. In some embodiments, this disclosure relates to vaccine and pharmaceutical compositions comprising an RSV G protein comprising the mutant or fusion protein arrangements disclosed herein. In some embodiments, this disclosure relates to virus particle / virus-like particle, nucleic acid, vector, or attenuated RSV vaccines reported herein for use. In some embodiments, this disclosure relates to methods for vaccinating, treating, or preventing RSV infection, including administering an effective amount of the compositions reported herein to a subject in need.

[0014] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, I49V, N81S, T87P, and / or R197K mutations.

[0015] In some embodiments, this disclosure relates to recombinant RSV G proteins comprising the following amino acid sequence:

[0016] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIV (SEQ ID NO: 27).

[0017] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0018] MSKNKDQRTAKTLERTWDTLNHLLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, Ga plus Ga in series (T-Ga / Ga)).

[0019] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0020] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNT (SEQ ID NO: 17, Ga 1-86).

[0021] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0022] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANKVTPTTAIIQDATSQIKNTPP (SEQ ID NO: 18, Ga 1-86 C-terminal PP).

[0023] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0024] PSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 19, Ga155-206).

[0025] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0026] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ IDNO: 1, Ga 1-86 plus 155-206 (Ga)).

[0027] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0028] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 5, group A 1-86 plus 150-210 plus group B 150-210, series Ga plus Gb (T-Ga / Gb)).

[0029] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence: KPTLKTPRL (SEQ ID NO:21, linker Gb).

[0030] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0031] QRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTPLLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 20, Ga 150-210 plus Gb 150-210).

[0032] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0033] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206).

[0034] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence: KPTTKQRQNK (SEQ ID NO: 28, Ga 145-154).

[0035] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence: CWAIAC (SEQ ID NO:22, Ga CX4C).

[0036] In some embodiments, the recombinant RSV G protein contains S177R and / or S177Q mutations.

[0037] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0038] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or

[0039] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q).

[0040] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0041] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQ (SEQ ID NO: 34, Ga 1-96).

[0042] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0043] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQLGISPSNPSE (SEQ ID NO: 35, Ga 1-106).

[0044] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0045] QRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLK (SEQ IDNO: 36, Ga 150-210).

[0046] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0047] TPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ IDNO: 37, Gb 150-210).

[0048] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0049] QRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTPLLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 20, Ga 150-210 plus Gb 150-210).

[0050] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0051] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO:5, Ga 1-86 plus Ga 150-210 plus Gb 150-210),

[0052] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210),

[0053] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQLGISPSNPSEQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-106 plus Ga 150-210 plus Gb 150-210) or

[0054] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 plus Gb 150-210).

[0055] In some embodiments, this disclosure relates to viral particles / virus-like particles containing any recombinant RSV G protein reported herein.

[0056] In some embodiments, this disclosure relates to nucleic acids encoding recombinant RSV proteins (e.g., G and / or F proteins) reported herein, which are operatively combined with heterologous promoters.

[0057] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0058] In some embodiments, this disclosure relates to attenuated RSV strains comprising the RSV G protein and / or RSV F protein reported herein.

[0059] In some embodiments, this disclosure relates to a vector comprising the nucleic acid reported herein or encoding the recombinant RSVG protein reported herein.

[0060] In some embodiments, this disclosure relates to methods of vaccinating against or treating RSV infection, methods comprising administering an effective amount of a vaccine or pharmaceutical composition to a subject in need, the vaccine or pharmaceutical composition comprising the RSV G protein, viral particles / virus-like particles, nucleic acids, attenuated RSV strains, or vectors reported herein.

[0061] In some embodiments, this disclosure relates to vaccine or pharmaceutical compositions comprising the RSV G protein, viral particles / virus-like particles, nucleic acids, attenuated RSV strains, attenuated RSV viruses, or vectors reported herein.

[0062] In some embodiments, this disclosure contemplates the use of the RSV G protein disclosed herein in combination with the RSV F protein having a stable pre-fusion construction / mutation.

[0063] In some embodiments, the vaccine or pharmaceutical composition is administered intranasally or intramuscularly. Brief description of the multiple perspectives in the attached diagram

[0064] Figure 1 The sequence alignments performed using BLASTP (NCBI) for the query (Q) of Ga 1-86 plus 155-206 (Ga) (SEQ ID NO: 1) and the target (S) of Ga CX4C 1-86 plus 145-206 (SEQ ID NO: 9) are shown. The difference is that Ga CX4C has an additional 10 amino acid peptide linker KPTTKQRQNK (SEQ ID NO: 28, Ga 145-154) and a variant sequence CWAIAC (SEQ ID NO: 22, Ga CX4C) between two cystine residues.

[0065] Figure 2 This study demonstrates sequence alignment using BLASTP (NCBI) for the query (Q) of Ga 1-86 plus 155-206 plus 155-206, tandem Ga plus Ga (T-Ga / Ga) (SEQ ID NO: 3) and the target (S) of group A 1-86 plus 150-210 (deleted Ga amino acids 87 to 149), plus group B 150-210 tandem Ga plus Gb (T-Ga / Gb) (SEQ ID NO: 5). The difference lies in the presence of an additional 5-amino acid peptide linker QRQNK (SEQ ID NO: 23), an additional 10-amino acid peptide linker KPTLKTPRL (SEQ ID NO: 21, linker Gb), the variant sequence NPPKKPKDDY (SEQ ID NO: 24), and the C-terminal segment GNNQLCKSICKT (SEQ ID NO: 25) containing the sequence CKSIC (SEQ ID NO: 26) between two cysteine ​​residues.

[0066] Figure 3Data on mouse antibody responses to RSV F+G protein VLPs with / without G peptide tandem repeats are shown. Bars represent antibody responses (absorbance) to F (F IgG), subgroup A G (Ga IgG), or subgroup B G (Gb IgG) proteins by enzyme immunoassay (EIA). Immunogens were control VLP (Ctl), pre-fusion stable F protein (F only), F plus Ga (aa 155-206. Ga1x), F plus Ga tandem repeat (Ga2x), and F plus Ga and Gb (aa 155-206) tandem repeats.

[0067] Figure 4 Data indicating the expression of functional pre-fusion F and G on VLP proteins (VLP, pre-fusion F alone, pre-fusion F, and Ga+b protein (as three different constructs: 1-86, 1-96, and 1-106)) are presented. Expression of the functional proteins was determined using Western blotting and ELISA assays (3D3 is an anti-G antibody, muvizumab is an anti-F antibody that recognizes both pre-fusion and post-fusion proteins, and D25 is an antibody that binds only to pre-fusion F).

[0068] Figure 5 Data are presented for immunization of Ga, Gb, and F using aluminum adjuvant and squalene oil-in-water emulsion adjuvant AddaS03 (containing squalene and DL-α-tocopherol, as well as the surfactant polysorbate 80 (Tween® 80), a sugar replaced with unsaturated long-chain fatty acids), and polyethylene glycol polymers (approximately 80 glycol units in total on average)). Compared to aluminum adjuvant, AddaS03 induced more potent antibody production and elicited higher serum titers.

[0069] Figure 6 Data from the neutralization assay are shown, indicating a high titer against the A2 virus.

[0070] Figure 7 Data indicating reduced lung viral load in vaccinated mice are presented – RSV gene was detected using qPCR measurements of homogenized lung tissue. In the control VLP group and with pre-fusion and G... 1-86 or G 1-96 Significant differences existed between the immunized groups. G 1-106 It induces neutralizing antibodies, in which the virus level rises. Detailed Implementation

[0071] Before describing this disclosure in more detail, it should be understood that this disclosure is not limited to the specific embodiments described, and therefore these can certainly be changed. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be restrictive, as the scope of this disclosure will be defined only by the appended claims.

[0072] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. While any methods and materials similar to or equivalent to those described herein may be used to implement or test this disclosure, preferred methods and materials are described hereafter.

[0073] All publications and patents cited in this specification are incorporated herein by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference, and the methods and / or materials disclosed and described in connection with the cited publications are incorporated herein by reference.

[0074] The “embodiments” in this disclosure refer to examples, but are not necessarily limited to such examples. As will be apparent to those skilled in the art, each of the individual embodiments described and illustrated herein has discrete components and features that can be readily separated from or combined with features of any other several embodiments without departing from the scope or spirit of this disclosure. Any method of narration may be performed in the order of the events described or in any other logically practicable order.

[0075] Unless otherwise stated, the embodiments disclosed herein employ techniques from medicine, organic chemistry, biochemistry, molecular biology, pharmacology, etc., which are within the scope of the art. These techniques are fully explained in the literature.

[0076] It should be noted that, as used in the specification and appended claims, the singular forms “a / an” and “the” include a plural of indicators unless the context clearly indicates otherwise. Throughout this specification and the following claims, numerous terms will be referenced, which should be defined as having the following meanings unless clearly intended to the contrary.

[0077] As used in this disclosure and one or more claims, the terms “comprising” (and any form of inclusion, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of inclusion, such as “includes” and “include)”), or “containing” (and any form of containing, such as “contains” and “contain)”) have the meanings conferred upon them by U.S. patent law because they are inclusive or open-ended and do not exclude additional unlisted elements or method steps.

[0078] When applied to the methods and compositions covered by this disclosure, "consistently made of" or "composed of" means those compositions as disclosed herein that exclude certain prior art elements to provide the inventive features of the claims, but may contain additional compositional components or method steps that do not substantially affect one or more essential and novel features of the composition or method.

[0079] “Nucleic acid” refers to a DNA molecule or an RNA molecule and is used synonymously with polynucleotides. Whenever this document refers to a nucleic acid or nucleic acid sequence encoding a specific protein and / or peptide, the nucleic acid or nucleic acid sequence preferably also includes a regulatory sequence that allows expression (i.e., transcription and / or translation of the nucleic acid sequence encoding the specific protein or peptide) in a suitable host (e.g., human).

[0080] An “amino acid sequence” is defined as a sequence consisting of any of the 20 naturally occurring amino acids, chemically modified amino acids, or synthetic amino acids. The terms “protein” and “peptide” refer to compounds containing amino acids linked by peptide bonds and are used interchangeably. As used herein, the “amino acid sequence” referred to herein means the amino acid sequence of a protein molecule. An “amino acid sequence” can be deduced from the nucleic acid sequence encoding a protein. Furthermore, unless the context requires otherwise, the terms “peptide” and “polypeptide” and “protein” are used interchangeably to refer to amino acids in which amino acid residues are linked by covalent peptide bonds, or alternatively (in the case of post-translational processing to remove internal fragments) by covalent disulfide bonds. Amino acid chains can be of any length and contain at least two or at least three amino acids; they can include protein domains or full-length proteins. Unless otherwise stated, the terms peptide, polypeptide, and protein also cover their various modified forms, including but not limited to glycosylated forms, phosphorylated forms, etc.

[0081] With respect to peptides having an amino acid sequence, the term "comprising" means a peptide that may contain additional N-terminal (amine-terminal) or C-terminal (carboxylate-terminal) amino acids; that is, the term is intended to include the amino acid sequence within a larger peptide. With respect to peptides having an amino acid sequence, the term "consisting of" means a peptide having a precise number of amino acids in the sequence and not exceeding or having an amino acid range expressly specified in the claims. In some embodiments, this disclosure contemplates "the N-terminus of the peptide is composed of an amino acid sequence," which means that the N-terminus of the peptide has a precise number of amino acids in the sequence and not exceeding or having an amino acid range specified in the claims, but the C-terminus may be linked to additional amino acids, for example, as part of a larger peptide. Similarly, this disclosure contemplates "the C-terminus of the peptide is composed of an amino acid sequence," which means that the C-terminus of the peptide has a precise number of amino acids in the sequence and not exceeding or having an amino acid range specified in the claims, but the N-terminus may be linked to additional amino acids, for example, as part of a larger peptide.

[0082] When referring to nucleic acid molecules, the term "recombinant" means a nucleic acid molecule that contains nucleic acid segments linked together using molecular biology techniques. When referring to proteins or peptides, the term "recombinant" means a protein molecule expressed using recombinant nucleic acid molecules.

[0083] As used in this article, “heterologous” genes, nucleic acids, promoters, antigens, proteins, etc., should be understood as nucleic acid or amino acid sequences that do not exist in naturally occurring nucleic acids or proteins.

[0084] The term "vector" or "expression vector" refers to a recombinant nucleic acid, either cellular or cell-free, containing the desired coding sequence and the appropriate nucleic acid sequence necessary for operatively linking the coding sequence in a specific host organism or expression system. In prokaryotes, the nucleic acid sequence necessary for expression typically includes a promoter, an operon (optional), and a ribosome-binding site, often along with other sequences. Eukaryotic cells are known to utilize promoters, enhancers, terminators, and polyadenylation signals.

[0085] A protein "expression system" refers to both in vivo (e.g., host cells) and in vitro (cell-free) systems. Systems for recombinant protein expression typically utilize somatic cells transfected with a DNA or mRNA expression vector containing a template. These cells are cultured under conditions that allow them to translate the desired protein. The expressed protein is extracted for subsequent purification. In vivo protein expression systems using prokaryotic and eukaryotic cells are well known. Proteins can be recovered using denaturing agents and protein refolding procedures. In vitro (cell-free) protein expression systems typically use translation-compatible extracts from whole cells or compositions containing sufficient components for transcription, translation, and optionally post-translational modifications, such as RNA polymerases, regulatory protein factors, transcription factors, ribosomes, tRNA cofactors, amino acids, and nucleotides. In the presence of an expression vector, these extracts and components can synthesize the target protein. Cell-free systems typically do not contain proteases and are capable of labeling proteins with modified amino acids. Some cell-free systems incorporate coding components for translation into the expression vector. See, for example, Shimizu et al., Cell-free translation reconstituted with purified components, 2001, Nat. Biotechnol, 19, 751-755 and Asahara and Chong, Nucleic Acids Research, 2010, 38(13): e141, both of which are hereby incorporated in their entirety by reference.

[0086] "Selective markers" are nucleic acids introduced into a recombinant vector encoding a polypeptide that confers a trait suitable for artificial selection or identification (reporter genes). For example, β-lactamases confer antibiotic resistance, enabling organisms expressing β-lactamases to survive in the presence of antibiotics in growth media. Another example is thymidine kinase, which makes the host selectively sensitive to ganciclovir. It can also be a selectable marker that allows differentiation between desired and unwanted cells based on the presence or absence of a desired color. For example, the lac-z gene produces β-galactosidase, which confers blue color in the presence of X-gal (5-bromo-4-chloro-3-indolyl-β-D-galactoside). If a recombinant insertion inactivates the lac-z gene, the resulting colonies are colorless. One or more selective markers can be present, for example, an enzyme that can supplement an expression of a specific compound required for the organism's growth (auxotrophic) that the organism cannot synthesize, and an enzyme that can convert the compound into another compound toxic to growth. URA3 (orotic acid nucleoside-5'-phosphate decarboxylase) is essential for uracil biosynthesis and can supplement the ura3 mutant, a uracil auxotroph. URA3 also converts 5-fluoroorotic acid into the toxic compound 5-fluorouracil. Other selective markers considered include any gene conferring antibacterial resistance or expressing fluorescent proteins. Examples include, but are not limited to, the following genes: ampr, camr, tetr, blast fungicide resistance gene, neor, hygr, abxr, neomycin phosphotransferase type II gene (nptII), p-glucuronidase (gus), green fluorescent protein (gfp), egfp, yfp, mCherry, p-galactosidase (lacZ), lacZa, lacZAM15, chloramphenicol acetyltransferase (cat), alkaline phosphatase (phoA), bacterial luciferase (luxAB), diammonium phosphate resistance gene (bar), phosphomannose isomerase (pmi), xylose isomerase (xylA), and azoxystrobin. Lapisitol dehydrogenase (atlD), UDP-glucose:galactose-1-phosphate uridine transferase I (galT), feedback-insensitive α-subunit of anthranilate synthase (OASA1D), 2-deoxyglucose (2-DOGR), benzyladenine-N-3-glucuronide, Escherichia coli threonine deaminase, glutamate 1-semialdehyde aminotransferase (GSA-AT), D-amino acid oxidase (DAAO), salt tolerance gene (rstB), ferroredoxin-like protein (pflp), trehalose-6-P synthase gene (AtTPS1), lysine racemic enzyme (lyr), dihydropyridine dicarboxylic acid synthase (dapA), tryptophan synthase β1 (AtTSB1), dehalogenase (dhlA), mannose-6-phosphate reductase gene (M6PR), hygromycin phosphotransferase (HPT), and D-serine amino lyase (dsdA).

[0087] “Labeling” refers to a detectable compound or composition that is conjugated directly or indirectly to another molecule (e.g., an antibody or protein) to facilitate the detection of that molecule. Specific, non-limiting examples of labeling include fluorescent tags, enzyme bonds, and radioisotopes. Labeling involves the incorporation of radiolabeled amino acids or the covalent attachment of a biotinylate moiety to a polypeptide that can be detected by a labeled avidin (e.g., streptavidin containing a fluorescent label or enzyme activity detectable by optical or colorimetric methods). Various methods for labeling polypeptides and glycoproteins are known in the art and can be used. Examples of peptide labeling include, but are not limited to, the following: radioisotopes or radionucleotides (e.g., 35S or 131I), fluorescent labels (e.g., fluorescein isothiocyanate (FITC), rhodamine, lanthanide phosphors), enzymatic labels (e.g., horseradish peroxidase, β-galactosidase, luciferase, alkaline phosphatase), chemiluminescent labels, biotinylated groups, predetermined peptide epitopes recognized by secondary reporter molecules (e.g., leucine zipper pairs, binding sites of secondary antibodies, metal-binding domains, epitope tags), or magnetic reagents (e.g., gadolinium chelates). In some embodiments, the label is attached via spacer arms of varying lengths to reduce potential steric hindrance.

[0088] In some embodiments, this disclosure relates to recombinant polypeptides comprising the sequences disclosed herein or variants or fusions thereof, wherein the amino-terminus or carbon-terminus of the amino acid sequence is optionally attached to a heterologous amino acid sequence, a label, or a reporter molecule.

[0089] In some embodiments, this disclosure relates to a recombinant vector comprising a nucleic acid encoding a polypeptide or chimeric protein thereof disclosed herein.

[0090] In some embodiments, the recombinant vector optionally includes a replication origin or gene associated with mammals, humans, insects, viruses, bacteria, bacterial plasmids, or yeast, such as a gene or a retroviral gene or a lentiviral LTR, TAR, RRE, PE, SLIP, CRS, and INS nucleotide segment or a gene selected from tat, rev, nef, vif, vpr, vpu, and vpx or a structural gene selected from gag, pol, and env.

[0091] In some embodiments, the recombinant vector optionally includes gene vector elements (nucleic acids), such as a selective marker region, a lac operon, a CMV promoter, a heterozygous chicken B-actin / CMV enhancer (CAG) operon, a tac operon, a T7 RNA polymerase operon, an SP6 RNA polymerase operon, an SV40 operon, an internal ribosome entry site (IRES) sequence, a cis-acting marmot postregulatory element (WPRE), a scaffold attachment region (SAR), an inverted terminal repeat (ITR), a FLAG tag coding region, a c-myc tag coding region, a metal affinity tag coding region, a streptavidin-binding peptide tag coding region, a polyhistidine tag coding region, a HA tag coding region, an MBP tag coding region, a GST tag coding region, a polyadenylation coding region, an SV40 polyadenylation signal, an SV40 origin of replication, and a Col E1 origin of replication, f1 origin, pBR322 origin, or pUC origin, TEV protease recognition site, loxP site, Cre recombinase coding region, or multiple cloning site (e.g., having 5, 6, or 7 or more restriction sites in a contiguous segment of less than 50 or 60 nucleotides or having 3 or 4 or more restriction sites in a contiguous segment of less than 20 or 30 nucleotides).

[0092] A “variant” is a polypeptide or polynucleotide that differs from a reference polypeptide or polynucleotide while retaining its essential characteristics. A typical variant of a polypeptide differs from another reference polypeptide in its amino acid sequence. Generally, the differences are limited, so the sequences of the reference polypeptide and the variant are generally very similar (homological) and identical in many regions. The amino acid sequences of the variant and the reference polypeptide may differ in one or more modifications (e.g., substitution, addition, and / or deletion). The substituted or inserted amino acid residues may or may not be amino acid residues encoded by the genetic code. Variants of a polypeptide may be naturally occurring (e.g., allelic variants) or may be variants known not to exist naturally.

[0093] Modifications and alterations can occur within the structure of the peptides disclosed herein, and still produce molecules with similar characteristics to the peptides (modifications and alterations, for example, are conserved amino acid substitutions). For instance, certain amino acids in the sequence can be substituted with other amino acids without a significant loss of activity. Because the biofunctional activity of a peptide is determined by its interacting abilities and properties, certain amino acid sequence substitutions can be made in the peptide sequence, but peptides with similar properties can still be obtained. Amino acid substitutions are generally based on the relative similarity of the amino acid side chain substituents, such as their hydrophobicity, hydrophilicity, charge, size, etc. Given that exemplary substitutions for one or more of the foregoing features are well known to those skilled in the art, and include, but are not limited to (original residue: exemplary substitution): (Ala substituted with Gly or Ser), (Arg substituted with Lys), (Asn substituted with Gln or His), (Asp substituted with Glu, Cys, or Ser), (Gln substituted with Asn), (Glu substituted with Asp), (Gly substituted with Ala), (His substituted with Asn or Gln), (Leu substituted with Ile or Val), (Lys substituted with Arg), (Met substituted with Leu or Tyr), (Ser substituted with Thr), (Thr substituted with Ser), (Trp substituted with Tyr), (Tyr substituted with Trp or Phe), and (Val substituted with Ile or Leu), the embodiments disclosed herein contemplate functional or biological equivalents of the peptides shown above. In some embodiments, the peptide variant is those peptide variants that have greater than 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 97%, and 99% sequence identity with the target peptide. Generally, the homologous peptides disclosed herein are characterized by having one or more amino acid substitutions, deletions, and / or additions.

[0094] "Identity" as known in the art refers to a relationship between two or more peptide sequences, as determined by comparing these sequences. In the art, "identity" also refers to the degree of sequence correlation between peptides, as determined by matching such sequence strings. "Identity" and "similarity" can be readily calculated using known methods. Preferred methods for determining identity have been designed to obtain the maximum match between test sequences. In some embodiments, sequence "identity" refers to the number (expressed as a percentage) of precisely paired amino acids in a sequence alignment between two aligned sequences, calculated using the larger of the number of identical positions divided by the shortest sequence length or the number of equivalent positions (excluding overhangs, where internal vacancies are counted as equivalent positions).

[0095] Methods for determining identity and similarity are incorporated into publicly available computer programs. The percentage of identity between two sequences can be determined using analysis software (Sequence Analysis Software Package of the Genetics Computer Group, Madison, Wisconsin), which incorporates Needelman and Wunsch (J MoI Biol [Journal of Molecular Biology], 48 443-453, 1970) algorithms (e.g., NBLAST and XBLAST). The US National Institutes of Health provides a website offering services for aligning two protein sequences using BLASTP (used to generate some of the sequence alignments disclosed herein). Default parameters are available for determining the identity of the peptides disclosed herein.

[0096] "Subject" refers to any animal, preferably a human patient, livestock, or domestic pet.

[0097] As used herein, the terms "treatment" (and "treating") are not limited to situations where the subject (e.g., a patient) is cured and the disease is eradicated. Rather, embodiments disclosed herein also contemplate treatments that merely alleviate symptoms and / or slow disease progression.

[0098] As used herein, the terms "prevent" and "preventing" include the prevention of recurrence, spread, or onset. This disclosure is not intended to limit it to complete prevention. In some embodiments, onset is delayed, or the severity of the disease is reduced.

[0099] As used herein, the term "viral particle" refers to virus-like particles, virions, or particles produced and / or separated by the replication of viruses (e.g., chimeric viruses, attenuated viruses).

[0100] As used herein, the term "virus-like particle" (VLP) refers to a viral core structure enclosed by a membrane containing viral envelope proteins. Furthermore, the viral core protein resides within the VLP's membrane. Typically, virus-like particles do not carry the genetic information encoding the proteins of the virus-like particle. Generally, virus-like particles lack a viral genome and are therefore non-infectious. Moreover, virus-like particles can often be produced in large quantities through heterologous expression and can be purified. Some virus-like particles may contain nucleic acids different from their genome. Typically, virus-like particles are non-replicating and non-infectious, lacking all or part of the viral genome, particularly the replicative and infectious components of the viral genome. As used herein, the term "virosome" refers to a viral particle similar to a virus-like particle, but differing in that it does not contain a viral core protein.

[0101] The term "chimeric respiratory syncytial virus" or "chimeric RSV" refers to nucleic acids containing sufficient RSV genes to enable the genome or antigenome to replicate in a host cell (e.g., Vero cells), and whose nucleic acid sequence is altered to include at least one nucleic acid segment structurally different from that of a naturally occurring RSV strain; that is, such that the nucleotide sequence of the RSV strain is not naturally present in the entire RSV genome. Chimeric respiratory syncytial viruses include RSV genes in which codons are altered to differ from those naturally occurring genes, although the polypeptides produced by RSV have the same amino acid sequence as those naturally expressed. Different RSV strains will have different nucleotide sequences and express proteins with different amino acid sequences but similar functions. Therefore, chimeric RSVs include RSV genes in which one or more genes from a substitute strain or a second strain are replaced, such that the nucleic acid sequence of the entire RSV genome is different from that of RSV found in nature. In some embodiments, chimeric RSVs include those strains that have nucleic acids deleted after the translation start codon to truncate protein expression, provided that such a truncation pattern is not found in the genome of naturally occurring RSV. In some embodiments, chimeric RSVs include those that are infectious but cannot replicate in human subjects.

[0102] When referring to polypeptides, the term "fusion" refers to the expression product of two or more coding sequences obtained from different sources. These coding sequences do not coexist in the natural environment but are cloned together and function as a single polypeptide sequence after translation. Fusion polypeptides are also called "hybrid" polypeptides. These coding sequences include those obtained from organisms of the same or different species.

[0103] RSV fusion protein (F) is a surface glycoprotein used for fusion with the target cell membrane. RSV fusion proteins exist in their pre-fusion conformation. The F protein is an RSV immunogen. Anti-RSV neutralizing antibodies typically target the pre-fusion conformation of the F protein. Mutations used to stabilize the pre-fusion F protein include S155C and S290C (for forming disulfide bonds (DS)), S190F and V207L ​​(for filling the cavity (Cav1)), and D486H, E487Q, F488W, and D489H (for forming a stable RSV F trimer (TriC)). See McLellan et al., Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus, Science. 2013, 342(6158): 592-598.

[0104] As used herein, “RSV G” protein or similar terminology refers to RSV attachment glycoprotein G and all its known variants or essential fragments. One example has the following amino acid sequence:

[0105] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAMIISTSLIIVAIIFIASANHKITSTTTIIQDATNQIKNTTPTYLTQNPQLGISPSNPSDITSLITTILDSTTPGVKSTLQSTTVGTKNTTTTQAQPNKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKRTTTKPTKKPTPKTTKKGPKPQTTKSKEAPTTKPTEEPTINTTKTNIITTLLTSNTTRNPELTSQMETFHSTSSEGNPSPSQVSITSEYPSQPSSPPNTPR (SEQ ID NO: 15, UniProtKB / Swiss-Protein accession number P27022.1) is an RSV G protein sequence, with the N-terminal methionine (M) at position 1. Other instances include login numbers P03423.1, CAA51765.1, AAD02944.1, CAA83874.1, AAD02941.1, CAA83870.1, P27021.1, AEO45938.1, CAA51761.1, CAA83871.1, AAU43727.1, AEO45918.1, AEO45888.1, AEO45878.1, AEO45849.1, AEC32086.1, AEQ98767.1, and AEQ63333. 1. Those specified in CAA83875.1, AEO45908.1, AEO45948.1, AEO45898.1, AEO45928.1, AAC36327.1, ACO83296.1, AEO45829.1, AEQ66845.1, ACI03570.1, AEO45868.1, P20895.2, AAD02943.1, AAX23993.1, AEQ66853.1, AEO45839.1, AEJ87998.1, and AEJ88006.1.

[0106] Throughout this specification, when referring to specific amino acid residues or regions in, for example, RSV F and G proteins, reference is made by referring to one or more amino acid residue numbers, which, unless otherwise stated, are based on the RSV amino acid sequences provided herein in the sequence listing and figures. It should be noted, and will be understood by those skilled in the art, that different RSV sequences may have different numbering systems, for example, if additional amino acid residues have been added or removed compared to SEQ ID NO: 15. Therefore, it should be understood that when a specific amino acid residue is referred to by a number, the description is not limited to the amino acid precisely located at that numbered position when counting from the beginning of the given amino acid sequence, but is intended for any and all RSV G sequences—even if the residue is not at the same precise numbered position, for example, if the RSV sequence is shorter or longer than SEQ ID NO: 15, or has insertions or deletions compared to SEQ ID NO: 15. Those skilled in the art can readily determine the amino acid position corresponding to / equivalent to any specific numbered residue listed herein, for example, by comparing a given RSV G sequence with SEQ ID NO: 15 or with any other RSV G amino acid sequence provided herein.

[0107] UniProtKB / Swiss-Prot: P03420.1 (SEQ ID NO: 16) provides the RSV F protein sequence, where the N-terminal methionine (M) is at position 1:

[0108] MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPPTNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEINLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGMDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN (SEQ ID NO: 16).

[0109] Prior to fusion, the RSV F protein variant DS-Cav1 (pF) has the following amino acid sequence:

[0110] (SEQ ID NO: 7).

[0111] This disclosure relates to compositions and methods for controlling respiratory syncytial virus (RSV) infection. In some embodiments, this disclosure relates to vaccine and pharmaceutical compositions comprising the RSV G protein, which comprises the mutant and / or fusion protein arrangements and F and / or pre-fusion F constructs / mutations reported herein. In some embodiments, this disclosure relates to the viral particle / virus-like particle, nucleic acid, vector, or attenuated RSV vaccines reported herein for use. In some embodiments, this disclosure relates to methods for vaccinating, treating, or preventing RSV infection, including administering an effective amount of the composition reported herein to a subject in need.

[0112] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, I49V, N81S, T87P, and / or R197K mutations.

[0113] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, and I49V mutations.

[0114] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, I49V, N81S, T87P, and R197K mutations.

[0115] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, and R197K mutations.

[0116] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, and T87P mutations.

[0117] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, and N81S mutations.

[0118] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, and I49V mutations.

[0119] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, and M48I mutations.

[0120] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, T87P, and R197K mutations.

[0121] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, N81S, and R197K mutations.

[0122] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, I49V, and R197K mutations.

[0123] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, and R197K mutations.

[0124] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, N81S, and T87P mutations.

[0125] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, I49V, and T87P mutations.

[0126] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, and T87P mutations.

[0127] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, I49V, and R197K mutations.

[0128] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, I49V, and T87P mutations.

[0129] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, I49V, and N81S mutations.

[0130] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, T87P, and R197K mutations.

[0131] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, N81S, and R197K mutations.

[0132] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, I49V, and R197K mutations.

[0133] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, and R197K mutations.

[0134] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, N81S, and T87P mutations.

[0135] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, I49V, and T87P mutations.

[0136] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, and T87P mutations.

[0137] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, I49V, and R197K mutations.

[0138] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, I49V, and T87P mutations.

[0139] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, I49V, and N81S mutations.

[0140] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, I49V, N81S, and R197K mutations.

[0141] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, I49V, T87P, and R197K mutations.

[0142] In some embodiments, this disclosure relates to recombinant RSV G proteins containing R15K, G29C, M48I, I49V, N81S, and T87P mutations.

[0143] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0144] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, tandem Ga plus Ga (T-Ga / Ga)) or a variant thereof.

[0145] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0146] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNT (SEQ ID NO: 17, Ga 1-86) or a variant thereof.

[0147] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0148] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANKVTPTTAIIQDATSQIKNTPP (SEQ ID NO: 18, Ga 1-86 C-terminal PP) or a variant thereof.

[0149] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence: PSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 19, Ga 155-206 (Ga)) or a variant thereof.

[0150] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0151] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ IDNO: 1, Ga 1-86 plus 155-206 (Ga)) or its variant.

[0152] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0153] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO:5, Group A 1-86 plus 150-210 plus Group B 150-210, Ga plus Gb in series (T-Ga / Gb)) or its variants.

[0154] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence: KPTLKTPRL (SEQ ID NO:21, linker Gb) or a variant thereof.

[0155] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0156] QRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTPLLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 20, Ga 150-210 plus Gb 150-210) or a variant thereof.

[0157] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0158] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206) or a variant thereof.

[0159] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence: KPTTKQRQNK (SEQ ID NO: 28, Ga 145-154) or a variant thereof.

[0160] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence: CWAIAC (SEQ ID NO:22, Ga CX4C) or a variant thereof.

[0161] In some embodiments, the recombinant RSV G protein contains S177R and / or S177Q mutations.

[0162] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0163] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or MSKNKDQRTAKTLERTWDTLNLLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206S177Q) or its variants.

[0164] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0165] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQ (SEQ ID NO: 34, Ga 1-96) or a variant thereof.

[0166] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0167] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQLGISPSNPSE (SEQ ID NO: 35, Ga 1-106) or a variant thereof.

[0168] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0169] QRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLK (SEQ ID NO: 36, Ga 150-210) or a variant thereof.

[0170] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0171] TPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 37, Gb 150-210) or a variant thereof.

[0172] QRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTPLLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 20, Ga 150-210 plus Gb 150-210) or a variant thereof.

[0173] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0174] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 5, Ga 1-86 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0175] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0176] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFH FEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0177] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0178] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQLGISPSNPSEQRQNKPPSKP NNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-106 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0179] In some embodiments, the recombinant RSV G protein comprises the following amino acid sequence:

[0180] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 plus Gb 150-210) or its variants.

[0181] In some embodiments, this disclosure relates to viral particles / virus-like particles containing any recombinant RSV G protein reported herein.

[0182] In some embodiments, this disclosure relates to nucleic acids encoding recombinant RSV proteins (e.g., G and / or F proteins) reported herein, which are operatively combined with heterologous promoters.

[0183] In some embodiments, the nucleic acid is RNA, mRNA, or DNA.

[0184] In some embodiments, this disclosure relates to live attenuated RSV strains comprising the RSV G protein and / or RSV F protein reported herein.

[0185] In some embodiments, this disclosure relates to a vector comprising the nucleic acid reported herein or encoding the recombinant RSVG protein reported herein.

[0186] In some embodiments, this disclosure relates to a vaccine or pharmaceutical composition or vaccine comprising the RSV G protein, viral particles / virus-like particles, nucleic acid, attenuated RSV strain, attenuated RSV virus, or vector reported herein.

[0187] In some embodiments, this disclosure relates to a G construct having a pre-fusion stable F (Fpre). In some embodiments, the unmutated form of the G construct is considered to reduce the immunogenicity of Fpre, while one or more of these mutations maintain and / or improve the immunogenicity of Fpre. In some embodiments, the G construct reported herein is considered to improve Fpre vaccines, thereby facilitating clinical use in young children, the elderly, or other immunocompromised patients.

[0188] RSV Ga tandem and pre-fusion F peptide

[0189] In some embodiments, this disclosure relates to peptides, virus-like particles (VLPs), or vaccine particles comprising an RSV G fusion peptide having the following amino acid sequence:

[0190] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ IDNO: 1, Ga 1-86 plus 155-206 (Ga)) or its variant.

[0191] In some embodiments, this disclosure relates to a nucleic acid encoding an RSV G fusion peptide having the following amino acid sequence:

[0192] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ IDNO: 1, Ga 1-86 plus 155-206 (Ga)) or its variant.

[0193] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0194] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV G fusion peptide having the following amino acid sequence:

[0195] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ IDNO: 1, Ga 1-86 plus 155-206 (Ga)) or its variant.

[0196] In some embodiments, the recombinant vector is an attenuated RSV strain encoding an RSV G fusion peptide having the following amino acid sequence:

[0197] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ IDNO: 1, Ga 1-86 plus 155-206 (Ga)) or its variant.

[0198] In some embodiments, the recombinant vector is an adenovirus vector or a modified vaccinia virus Ankara strain (MVA).

[0199] In some embodiments, this disclosure relates to attenuated RSV strains, recombinant vectors, or nucleic acids comprising the following nucleic acid sequences:

[0200] ATGAGCAAGAACAAGGACCAGCGGACCGCCAAGACACTGGAAAGAACCTGGGACACCCTGAACCATCTGCTGTTCATCAGCAGCTGCCTGTACAAGCTGAACCTGAAGTCTGTGGCCCAGATCACCCTGAGCATCCTGGCCATCGTGATCAGCACCAGCCTGATCATTGCCGCCATCATCTTTATCGCCAGCGCCAACCACAAAGTGAC CCCTACCACAGCCATCATCCAGGACGCCACAAGCCAGATCAAGAAACCCCTCCAAGCAAGCCCAACAACGACTTCCACTTCGAGGTGTTCAACTTCGTGCCCTGCAGCATCTGCAGCAACAATCCTACCTGCTGGGCCATCTGCAAGAGAATCCCCAACAAGAAGCCCGGCAAAAAGACCACCACAAAGCCCACAAAGAAGCCC (SEQ ID NO: 2, Ga).

[0201] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0202] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ IDNO: 1, Ga 1-86 plus 155-206 (Ga)) or its variant.

[0203] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0204] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 1, Ga 1-86 plus 155-206 (Ga)) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0205] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0206] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0207] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ IDNO: 1, Ga 1-86 plus 155-206 (Ga)) or its variant.

[0208] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0209] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 1, Ga 1-86 plus 155-206 (Ga)) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0210] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0211] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0212] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0213] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ IDNO: 1, Ga 1-86 plus 155-206 (Ga)) or its variant.

[0214] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0215] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 1, Ga 1-86 plus 155-206 (Ga)) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0216] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0217] In some embodiments, this disclosure relates to a recombinant vector comprising an attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0218] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ IDNO: 1, Ga 1-86 plus 155-206 (Ga)) or its variant.

[0219] In some embodiments, the recombinant vector is an attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide, the RSV fusion peptide having the following amino acid sequence:

[0220] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 1, Ga 1-86 plus 155-206 (Ga)) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0221] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0222] In some embodiments, this disclosure relates to a recombinant vector, which is an adenovirus vector or a recombinant modified vaccinia virus Ankara strain (MVA).

[0223] In some embodiments, this disclosure relates to attenuated RSV strains, recombinant vectors, or nucleic acids comprising the following nucleic acid sequences:

[0224]

[0225] RSV T-Ga / Ga

[0226] In some embodiments, this disclosure relates to peptides, virus-like particles (VLPs), or vaccine particles comprising an RSV G fusion peptide having the following amino acid sequence:

[0227] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, tandem Ga plus Ga (T-Ga / Ga)) or a variant thereof.

[0228] In some embodiments, this disclosure relates to a nucleic acid encoding an RSV G fusion peptide having the following amino acid sequence:

[0229] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, tandem Ga plus Ga (T-Ga / Ga)) or a variant thereof.

[0230] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0231] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV G fusion peptide having the following amino acid sequence:

[0232] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, tandem Ga plus Ga (T-Ga / Ga)) or a variant thereof.

[0233] In some embodiments, the recombinant vector is a live attenuated RSV strain encoding an RSV G fusion peptide having the following amino acid sequence:

[0234] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, tandem Ga plus Ga (T-Ga / Ga)) or a variant thereof.

[0235] In some embodiments, the recombinant vector is an adenovirus vector or a recombinant modified vaccinia virus Ankara strain (MVA).

[0236] In some embodiments, this disclosure relates to attenuated RSV strains, recombinant vectors, or nucleic acids comprising the following nucleic acid sequences:

[0237] (SEQ ID NO: 4, (T-Ga / Ga)).

[0238] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0239] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, tandem Ga plus Ga (T-Ga / Ga)) or a variant thereof.

[0240] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0241] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, tandem Ga plus Ga (T-Ga / Ga)) or variants thereof, and the RSV F peptide has the following amino acid sequence:

[0242] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0243] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0244] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, tandem Ga plus Ga (T-Ga / Ga)) or a variant thereof.

[0245] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0246] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, tandem Ga plus Ga (T-Ga / Ga)) or variants thereof, and the RSV F peptide has the following amino acid sequence:

[0247] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0248] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0249] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0250] MSKNKDQRTAKTLERTWDTLNHLLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, Ga plus Ga in series (T-Ga / Ga)).

[0251] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0252] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, tandem Ga plus Ga (T-Ga / Ga)) or variants thereof, and the RSV F peptide has the following amino acid sequence:

[0253] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0254] In some embodiments, the recombinant vector is an attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide, the RSV fusion peptide having the following amino acid sequence:

[0255] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, tandem Ga plus Ga (T-Ga / Ga)) or a variant thereof.

[0256] In some embodiments, the recombinant vector is an attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide, the RSV fusion peptide having the following amino acid sequence:

[0257] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 3, Ga 1-86 plus 155-206 plus 155-206, tandem Ga plus Ga (T-Ga / Ga)) or variants thereof, and the RSV F peptide has the following amino acid sequence:

[0258] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0259] RSV T-Ga / Gb

[0260] In some embodiments, this disclosure relates to peptides, virus-like particles (VLPs), or vaccine particles comprising an RSV G fusion peptide having the following amino acid sequence:

[0261] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO:5, Group A 1-86 plus 150-210 plus Group B 150-210, Ga plus Gb in series (T-Ga / Gb)) or its variants.

[0262] In some embodiments, this disclosure relates to a nucleic acid encoding an RSV G fusion peptide having the following amino acid sequence:

[0263] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO:5, Group A 1-86 plus 150-210 plus Group B 150-210, Ga plus Gb in series (T-Ga / Gb)) or its variants.

[0264] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0265] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV G fusion peptide having the following amino acid sequence:

[0266] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO:5, Group A 1-86 plus 150-210 plus Group B 150-210, Ga plus Gb in series (T-Ga / Gb)) or its variants.

[0267] In some embodiments, the recombinant vector is an attenuated RSV strain encoding an RSV G fusion peptide having the following amino acid sequence:

[0268] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO:5, Group A 1-86 plus 150-210 plus Group B 150-210, Ga plus Gb in series (T-Ga / Gb)) or its variants.

[0269] In some embodiments, the recombinant vector is an adenovirus vector recombinant or modified vaccinia virus Ankara strain (MVA).

[0270] In some embodiments, the attenuated RSV strain, recombinant vector, or nucleic acid comprises the following nucleic acid sequences:

[0271] (SEQ ID NO: 6, (T-Ga / Gb)).

[0272] In some embodiments, this disclosure relates to peptides, virus-like particles (VLPs), or vaccine particles comprising an RSV G fusion peptide having the following amino acid sequence:

[0273] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 5, Ga 1-86 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0274] In some embodiments, this disclosure relates to a nucleic acid encoding an RSV G fusion peptide having the following amino acid sequence:

[0275] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 5, Ga 1-86 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0276] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0277] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV G fusion peptide having the following amino acid sequence:

[0278] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 5, Ga 1-86 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0279] In some embodiments, this disclosure relates to a live attenuated RSV strain encoding an RSV G fusion peptide having the following amino acid sequence:

[0280] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 5, Ga 1-86 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0281] In some embodiments, this disclosure relates to attenuated RSV strains, recombinant vectors, or nucleic acids comprising the following nucleic acid sequences:

[0282] (SEQ ID NO: 31, Ga / Ga / Gb).

[0283] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0284] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 5, Ga 1-86 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0285] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0286] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO:5, Ga 1-86 plus Ga 150-210 plus Gb 150-210) or variants thereof, and the RSV F peptide has the following amino acid sequence:

[0287] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0288] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0289] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 5, Ga 1-86 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0290] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0291] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO:5, Ga 1-86 plus Ga 150-210 plus Gb 150-210) or variants thereof, and the RSV F peptide has the following amino acid sequence:

[0292] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0293] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0294] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0295] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 5, Ga 1-86 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0296] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0297] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO:5, Ga 1-86 plus Ga 150-210 plus Gb 150-210) or variants thereof, and the RSV F peptide has the following amino acid sequence:

[0298] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0299] In some embodiments, this disclosure relates to an attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide, the RSV fusion peptide having the following amino acid sequence:

[0300] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 5, Ga 1-86 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0301] In some embodiments, this disclosure relates to an attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide, the RSV fusion peptide having the following amino acid sequence:

[0302] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO:5, Ga 1-86 plus Ga 150-210 plus Gb 150-210) or variants thereof, and the RSV F peptide has the following amino acid sequence:

[0303] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0304] In some embodiments, this disclosure relates to peptides, virus-like particles (VLPs), or vaccine particles comprising an RSV G fusion peptide having the following amino acid sequence:

[0305] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFH FEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0306] In some embodiments, this disclosure relates to a nucleic acid encoding an RSV G fusion peptide having the following amino acid sequence:

[0307] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFH FEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0308] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0309] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV G fusion peptide having the following amino acid sequence:

[0310] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFH FEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0311] In some embodiments, this disclosure relates to a live attenuated RSV strain encoding an RSV G fusion peptide having the following amino acid sequence:

[0312] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFH FEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0313] In some embodiments, this disclosure relates to attenuated RSV strains, recombinant vectors, or nucleic acids comprising the following nucleic acid sequences:

[0314] (SEQ ID NO: 32).

[0315] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0316] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFH FEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0317] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0318] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210) or variants thereof, and the RSV F peptide has the following amino acid sequence:

[0319] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0320] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0321] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFH FEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0322] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0323] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210) or variants thereof, and the RSV F peptide has the following amino acid sequence:

[0324] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0325] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0326] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0327] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFH FEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0328] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0329] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210) or variants thereof, and the RSV F peptide has the following amino acid sequence:

[0330] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0331] In some embodiments, this disclosure relates to an attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide, the RSV fusion peptide having the following amino acid sequence:

[0332] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFH FEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210) or a variant thereof.

[0333] In some embodiments, this disclosure relates to an attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide, the RSV fusion peptide having the following amino acid sequence:

[0334] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 29, Ga 1-96 plus Ga 150-210 plus Gb 150-210) or variants thereof, and the RSV F peptide has the following amino acid sequence:

[0335] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0336] In some embodiments, this disclosure relates to peptides, virus-like particles (VLPs), or vaccine particles comprising an RSV G fusion peptide having the following amino acid sequence:

[0337] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 plus Gb 150-210) or its variants.

[0338] In some embodiments, this disclosure relates to a nucleic acid encoding an RSV G fusion peptide having the following amino acid sequence:

[0339] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 plus Gb 150-210) or its variants.

[0340] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0341] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV G fusion peptide having the following amino acid sequence:

[0342] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 plus Gb 150-210) or its variants.

[0343] In some embodiments, this disclosure relates to a live attenuated RSV strain encoding an RSV G fusion peptide having the following amino acid sequence:

[0344] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 plus Gb 150-210) or its variants.

[0345] In some embodiments, this disclosure relates to attenuated RSV strains, recombinant vectors, or nucleic acids comprising the following nucleic acid sequences:

[0346] ATGAGCAAGAACAAGGACCAGCGGACCGCCAAGACACTGGAAAGAACCTGGGACACCCTGAACCATCTGCTGTTCATCAGCAGCTGCCTGTACAAGCTGAACCTGAAGTCTGTGGCCCAGATCACCCTGAGCATCCTGGCCATCGTGATCAGCACCAGCCTGATCATTGCCGCCATCATCTTTATCGCCAGCGCCAACCACAAAGTGACCCCTACCACAGCCATCATCCAGGACGCCACAAGCCAGATCAAGAACACCCAGAGACAGAACAAGCCTCCAAGCAAGCCCAACAACGACTTCCACTTCGAGGTGTTCAACTTCGTGCCCTGCAGCATCTGCAGCAACAATCCTACCTGCTGGGCCATCTGCAAGAGAATCCCCAACAAGAAGCCCGGCAAAAAGACCACCACAAAGCCCACAAAGAAGCCCACACTGAAAACCCCTCGGCTGAAGAACCCTCCTAAGAAGCCCAAGGACGACTACCACTTCGAGGTGTTCAACTTCGTGCCCTGCAGCATCTGCGGCAACAACCAGCTGTGCAAGAGCATCTGCAAGACAATCCCCAGCAACAAGCCAAAGAAGAAGCCTACCATCAAGCCCACAAACAAACCCACCACCAAGACCCAGAGACAGAACAAGCCTCCAAGCAAGCCCAACAACGACTTCCACTTCGAGGTGTTCAACTTCGTGCCCTGCAGCATCTGCAGCAACAATCCTACCTGCTGGGCCATCTGCAAGAGAATCCCCAACAAGAAGCCCGGCAAAAAGACCACCACAAAGCCCACAAAGAAGCCCACACTGAAAACCCCTCGGCTGAAGAACCCTCCTAAGAAGCCCAAGGACGACTACCACTTCGAGGTGTTCAACTTCGTGCCCTGCAGCATCTGCGGCAACAACCAGCTGTGCAAGAGCATCTGCAAGACAATCCCCAGCAACAAGCCAAAGAAGAAGCCTACCATCAAGCCCACAAACAAACCCACCACCAAGACC(SEQ IDNO: 33, Ga / Gb / Ga / Gb).

[0347] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0348] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 plus Gb 150-210) or its variants.

[0349] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0350] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 Gb (or a variant thereof), and the RSV F peptide has the following amino acid sequence:

[0351] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0352] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0353] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 plus Gb 150-210) or its variants.

[0354] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0355] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 Gb (or a variant thereof), and the RSV F peptide has the following amino acid sequence:

[0356] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0357] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0358] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0359] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 plus Gb 150-210) or its variants.

[0360] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0361] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 Gb (or a variant thereof), and the RSV F peptide has the following amino acid sequence:

[0362] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0363] In some embodiments, this disclosure relates to an attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide, the RSV fusion peptide having the following amino acid sequence:

[0364] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 plus Gb 150-210) or its variants.

[0365] In some embodiments, this disclosure relates to an attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide, the RSV fusion peptide having the following amino acid sequence:

[0366] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFN FVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKTQRQNKPPSKPNNDFHFEFVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 30, Ga 1-86 plus Ga 150-210 plus Gb 150-210 plus Ga 150-210 Gb (or a variant thereof), and the RSV F peptide has the following amino acid sequence:

[0367] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0368] RSV Ga CX4C

[0369] In some embodiments, this disclosure relates to peptides, virus-like particles (VLPs), or vaccine particles comprising an RSV G fusion peptide having the following amino acid sequence:

[0370] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206) or a variant thereof.

[0371] In some embodiments, this disclosure relates to a nucleic acid encoding an RSV G fusion peptide having the following amino acid sequence:

[0372] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206) or a variant thereof.

[0373] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0374] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV G fusion peptide having the following amino acid sequence:

[0375] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206) or a variant thereof.

[0376] In some embodiments, the recombinant vector is an attenuated RSV strain encoding an RSV G fusion peptide having the following amino acid sequence:

[0377] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206) or a variant thereof.

[0378] In some embodiments, the recombinant vector is an adenovirus vector or a recombinant modified vaccinia virus Ankara strain (MVA).

[0379] In some embodiments, the attenuated RSV strain, recombinant vector, or nucleic acid comprises the following nucleic acid sequences:

[0380] ATGAGCAAGAACAAGGACCAGCGGACCGCCAAGACACTGGAAAGAACCTGGGACACCCTGAACCATCTGCTGTTCATCAGCAGCTGCCTGTACAAGCTGAACCTGAAGTCTGTGGCCCAGATCACCCTGAGCATCCTGGCCATCGTGATCAGCACCAGCCTGATCATTGCCGCCATCATCTTTATCGCCAGCGCCAACCACAAAGTGACCCCTACCACAGCCATC ATCCAGGACGCCACAAGCCAGATCAAGAACACCAAGCCTACCACCAAGCAGAGACAGAACAAGCCTCCAAGCAAGCCCAACAACGACTTCCACTTCGAGGTGTTCAACTTCGTGCCCTGCAGCATCTGCAGCAACAATCCTACCTGCTGGGCCATCGCCTGCAAGAGAATCCCCAACAAGAAGCCCGGCAAAAAGACCACCACAAAGCCCACAAAGAAGCCC (SEQ ID NO: 10, Ga CX4C).

[0381] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0382] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206) or a variant thereof.

[0383] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0384] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0385] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0386] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0387] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206) or a variant thereof.

[0388] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0389] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0390] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0391] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0392] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0393] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206) or a variant thereof.

[0394] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0395] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0396] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0397] In some embodiments, the recombinant vector is an attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide, the RSV fusion peptide having the following amino acid sequence:

[0398] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206) or a variant thereof.

[0399] In some embodiments, the attenuated RSV strain encodes an RSV F peptide and an RSV G fusion peptide, the RSV G fusion peptide having the following amino acid sequence:

[0400] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0401] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0402] RSV Ga 145 S177R

[0403] In some embodiments, this disclosure relates to peptides, virus-like particles (VLPs), or vaccine particles comprising an RSV G fusion peptide having the following amino acid sequence:

[0404] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or its variants.

[0405] In some embodiments, this disclosure relates to a nucleic acid encoding an RSV G fusion peptide having the following amino acid sequence:

[0406] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or its variants.

[0407] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0408] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV G fusion peptide having the following amino acid sequence:

[0409] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or its variants.

[0410] In some embodiments, this disclosure relates to a live attenuated RSV strain encoding an RSV G fusion peptide having the following amino acid sequence:

[0411] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or its variants.

[0412] In some embodiments, this disclosure relates to attenuated RSV strains, recombinant vectors, or nucleic acids comprising the following nucleic acid sequences:

[0413] ATGAGCAAGAACAAGGACCAGCGGACCGCCAAGACACTGGAAAGAACCTGGGACACCCTGAACCATCTGCTGTTCATCAGCAGCTGCCTGTACAAGCTGAACCTGAAGTCTGTGGCCCAGATCACCCTGAGCATCCTGGCCATCGTGATCAGCACCAGCCTGATCATTGCCGCCATCATCTTTATCGCCAGCGCCAACCACAAAGTGACCCCTACCACAGCCATC ATCCAGGACGCCACAAGCCAGATCAAGAACACCAAGCCTACCACCAAGCAGAGACAGAACAAGCCTCCAAGCAAGCCCAACAACGACTTCCACTTCGAGGTGTTCAACTTCGTGCCCTGCAGCATCTGCAGAAACAATCCTACCTGCTGGGCCATCTGCAAGAGAATCCCCAACAAGAAGCCCGGCAAAAAGACCACCACAAAGCCCACAAAGAAGCCC (SEQID NO: 12, Ga S177R).

[0414] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0415] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or its variants.

[0416] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0417] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0418] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0419] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0420] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or its variants.

[0421] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0422] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0423] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0424] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0425] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0426] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or its variants.

[0427] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0428] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0429] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0430] In some embodiments, this disclosure relates to a live attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0431] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or its variants.

[0432] In some embodiments, this disclosure relates to a live attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0433] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0434] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0435] RSV Ga 145 S177Q

[0436] In some embodiments, this disclosure relates to peptides, virus-like particles (VLPs), or vaccine particles comprising an RSV G fusion peptide having the following amino acid sequence:

[0437] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFFEVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q) or its variants.

[0438] In some embodiments, this disclosure relates to a nucleic acid encoding an RSV G fusion peptide having the following amino acid sequence:

[0439] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFFEVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q) or its variants.

[0440] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0441] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV G fusion peptide having the following amino acid sequence:

[0442] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFFEVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q) or its variants.

[0443] In some embodiments, this disclosure relates to a live attenuated RSV strain encoding an RSV G fusion peptide having the following amino acid sequence:

[0444] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFFEVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q) or its variants.

[0445] In some embodiments, this disclosure relates to attenuated RSV strains, recombinant vectors, or nucleic acids comprising the following nucleic acid sequences:

[0446] ATCCCGCCACCATGAGCAAGAACAAGGACCAGCGGACCGCCAAGACACTGGAAAGAACCTGGGACACCCTGAACCATCTGCTGTTCATCAGCAGCTGCCTGTACAAGCTGAACCTGAAGTCTGTGGCCCAGATCACCCTGAGCATCCTGGCCATCGTGATCAGCACCAGCCTGATCATTGCCGCCATCATCTTTATCGCCAGCGCCAACCACAAAGTGACCCCTACCACA GCCATCATCCAGGACGCCACAAGCCAGATCAAGAACACCAAGCCTACCACCAAGCAGAGACAGAACAAGCCTCCAAGCAAGCCCAACGACTTCCACTTCGAGGTGTTCAACTTCGTGCCCTGCAGCATCTGCCAGAACAATCCTACCTGCTGGGCCATCTGCAAGAGAATCCCCAACAAGAAGCCCGGCAAAAAGACCACCACAAAGCCCACAAAGAAGCCC (SEQ ID NO: 14, Ga S177Q).

[0447] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0448] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFFEVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q) or its variants.

[0449] In some embodiments, this disclosure relates to virus-like particles (VLPs) or vaccine particles comprising an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0450] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0451] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0452] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0453] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFFEVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q) or its variants.

[0454] In some embodiments, this disclosure relates to nucleic acids encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0455] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0456] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0457] In some embodiments, the nucleic acid is mRNA, RNA, or DNA.

[0458] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0459] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFFEVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q) or its variants.

[0460] In some embodiments, this disclosure relates to a recombinant vector encoding an RSV F peptide and an RSV G fusion peptide having the following amino acid sequence:

[0461] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0462] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0463] In some embodiments, this disclosure relates to an attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide, the RSV fusion peptide having the following amino acid sequence:

[0464] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFFEVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q) or its variants.

[0465] In some embodiments, this disclosure relates to an attenuated RSV strain encoding an RSV F peptide and an RSV G fusion peptide, the RSV fusion peptide having the following amino acid sequence:

[0466] MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q) or a variant thereof, and the RSV F peptide has the following amino acid sequence:

[0467] (SEQ ID NO: 7, F DS-Cav1 (pF) before fusion) or a variant thereof.

[0468] Vaccination methods

[0469] In some embodiments, this disclosure relates to methods of vaccinating against or treating RSV infection, methods comprising administering an effective amount of a vaccine or pharmaceutical composition to a subject in need, the vaccine or pharmaceutical composition comprising the RSV G protein, viral particles / virus-like particles, nucleic acids, attenuated RSV strains, or vectors reported herein.

[0470] In some embodiments, this disclosure relates to methods of vaccinating against or treating RSV infection, methods comprising administering an effective amount of a vaccine or pharmaceutical composition to a subject in need, the vaccine or pharmaceutical composition comprising the RSV G protein, viral particles / virus-like particles, nucleic acids, attenuated RSV strains, or vectors reported herein.

[0471] In some embodiments, the subjects are premature infants, newborns, infants, the elderly, or immunocompromised individuals.

[0472] In some embodiments, the subject is a person aged 2, 12, or 16 years or older. In some embodiments, the subject is a person aged 2, 12, or 15 years, or younger than 2, 12, or 16 years. In some embodiments, the subject is a person aged 55 or 65 years or older. In some embodiments, the subject is a human subject who is an infant (e.g., one month to two years old). In some embodiments, the subject is a human subject who is a child (e.g., two to twelve years old). In some embodiments, the subject is a human subject who is an adolescent (e.g., twelve to sixteen years old). In some embodiments, the subject is a person aged sixteen years or older.

[0473] In some embodiments, the subject has an impaired immune system due to the need to maintain immunosuppressive therapy, for example, the subject has or has been diagnosed with Digeorg syndrome, Wiscot-Aldrich syndrome, Bruton's agammaglobulinemia, the subject is receiving chemotherapy or radiation therapy due to a diagnosis of cancer, the subject is receiving corticosteroids due to a diagnosis of rheumatoid arthritis, lupus, vasculitis, or the subject is a solid organ recipient for the purpose of preventing organ transplant rejection.

[0474] Pharmaceutical Composition

[0475] In some embodiments, this disclosure relates to a vaccine or pharmaceutical composition or vaccine comprising the RSV G protein, viral particles / virus-like particles, nucleic acid, attenuated RSV strain, attenuated RSV virus, or vector reported herein. Pharmaceutical compositions provided herein may generally comprise one or more pharmaceutically acceptable and / or approved carriers, additives, antibiotics, preservatives, adjuvants, diluents, and / or stabilizers. Such excipients may be water, saline, glycerol, ethanol, wetting agents or emulsifiers, pH buffers, etc. Suitable carriers are typically large, slowly metabolizing molecules such as proteins, polysaccharides, polylactic acid, polyglycolic acid, polymeric amino acids, amino acid copolymers, lipid aggregates, etc.

[0476] A vaccine is typically understood as a prophylactic or therapeutic material that provides at least one antigen or antigenic function. Typically, a vaccine comprises a conventional saline or buffered aqueous solution medium in which the composition is suspended or dissolved. Upon introduction into a host, the vaccine elicits an immune response, including but not limited to the production of antibodies and / or cytokines, and / or the activation of cytotoxic T cells, antigen-presenting cells, helper T cells, dendritic cells, and / or other cellular responses.

[0477] In some embodiments, the vaccine optionally includes an adjuvant, i.e., a nonspecific immune response stimulant or a substance that allows the formation of a reservoir in the host, providing an even stronger immune response when the adjuvant is combined with the vaccine. Examples include incomplete Freund's adjuvant and aluminum hydroxide.

[0478] In some embodiments, the vaccine is a nucleic acid, recombinant vector, or attenuated vaccine, such as a DNA, RNA, or mRNA-based vaccine (encoding one or more peptide antigens disclosed herein, the peptide antigen having at least one open reading frame, which can be translated by a cell or organism provided with nucleic acid, DNA, RNA, or mRNA). If more than one protein is translated, the protein may be expressed in a single vector / nucleic acid or in multiple separate nucleic acid(s) / vectors. The translation product is a peptide or protein disclosed herein or a viral particle containing one or more such proteins, which may serve as an antigen, preferably as an immunogen. The product may also be a fusion protein consisting of more than one immunogen, such as a fusion protein having two or more peptides or proteins derived from the same or different viral proteins, wherein these peptides or proteins are optionally linked by self-cleaving linker sequences.

[0479] In some embodiments, nucleic acids, DNA, RNA, or mRNA can be programmed to have two (bicistronic) or more (polycistronic) open reading frames (ORFs). In this context, an open reading frame is a sequence that includes a start codon, which can be used as the starting position for translating the encoded nucleic acid into a peptide or protein. Translation of one or more such nucleic acids produces two (bicistronic) or more (polycistronic) different translation products / proteins (provided the ORFs are not identical). For expression in eukaryotes, such nucleic acids may include an internal ribosome entry site (IRES) sequence, which allows the expression of two or more proteins on a single nucleic acid molecule.

[0480] In some embodiments, peptides, viral particles, virus-like particles, nucleic acids, recombinant vectors, or attenuated vaccines can be administered naked without association with any other mediator.

[0481] In some embodiments, peptides, viral particles, virus-like particles, nucleic acids, recombinant vectors, or attenuated vaccines may be administered in a pharmaceutical composition having pharmaceutically acceptable excipients selected from: lactose, sucrose, mannitol, triethyl citrate, dextran, cellulose, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, carboxymethylcellulose, croscarmellose sodium, polyvinylpyrrolidone, crospovidone, ethylcellulose, povidone, methyl acrylate and ethyl acrylate copolymers, polyethylene glycol, sorbitan fatty acid esters, dodecyl sulfate, gelatin, glycerol, glyceryl monooleate, silica, titanium dioxide, talc, corn starch, carnauba wax, stearic acid, sorbic acid, magnesium stearate, calcium stearate, castor oil, mineral oil, calcium phosphate, starch, starch carboxymethyl ether, iron oxide, triacetin, gum arabic, its esters or salts.

[0482] In some embodiments, the pharmaceutical composition is in the form of a sterile pH-buffered saline solution or a phosphate buffer solution with a pH of 6 to 8, optionally containing sugars or polysaccharides.

[0483] In some embodiments, pharmaceutically acceptable excipients are cationic or polycationic compounds and / or have a polymer carrier. In some embodiments, peptides, viral particles, virus-like particles, nucleic acids, recombinant vectors, or attenuated RSV are present in the pharmaceutical composition, which is associated or complexed with a cationic or polycationic compound or polymer carrier and optionally an adjuvant. In some embodiments, the cationic or polycationic compound is protamine, spermine, spermidine, poly-L-lysine (PLL), poly-histidine or poly-arginine, cationic polysaccharides (e.g., chitosan), polygluconine, cationic polymers, polyethyleneimine (PEI), homopolymers and copolymers of lactic acid and glycolic acid, or polymethyl methacrylate.

[0484] In some embodiments, peptides, viral particles, virus-like particles, nucleic acids, recombinant vectors, or attenuated RSV may be included in the pharmaceutical composition with an adjuvant, or administered in combination with an adjuvant. Adjuvants considered suitable for storage and delivery include cationic or polycationic compounds, liposomes, chitosan, aluminum adjuvant solutions, aluminum hydroxide, aluminum salts, aluminum phosphate gel, aluminum hydroxide gel (aluminum adjuvant), polyphosphazene, squalene, squalene emulsions, CpG oligonucleotides (nucleic acids containing unmethylated CpG motifs), 1-α,25-dihydroxyvitamin D3, calcium phosphate gel, dimethyloctadecyl ammonium bromide, dehydroepiandrosterone, myristoylphosphatidylcholine, myristoylphosphatidylglycerol, sodium deoxycholate, imiquimod, interferon-γ, interleukin-1β, and leukocytes. Interleukin-2, Interleukin-7, Interleukin-12, 7-Allyl-8-oxoguanosine, Acetylmurayl-alanyl-isoglutamine, N-Acetylmurayl-L-threonyl-D-isoglutamine, NAc-Mur-L-Ala-D-Gln-OCH3, QS-21, Quil-A (Quil-A saponin), Sorbitan trioleate, 2,6,10,15,19,23-hexamethyltetracosane, Stearoyltyrosine, Lipid A, 4′-Monophosphoryllipid A, 3-O-deacylated-4′-monophosphoryllipid A (MPL) TM ), liposomes containing lipid A, and lipid A adsorbed on aluminum hydroxide.

[0485] Pharmaceutically acceptable carriers that can be used in these compositions include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, albumin (e.g., human serum albumin), buffering substances (e.g., phosphates, glycine, sorbic acid, citric acid, potassium sorbate), mixtures of partial glycerides of saturated vegetable fatty acids, water, salts or electrolytes (e.g., protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts), colloidal silica, magnesium trisilicate, hydrophilic polymers (e.g., polyvinylpyrrolidone), cellulose-based substances, polyethylene glycol, sodium carboxymethyl cellulose, polyacrylates, waxes, gelatin, polyethylene polyoxypropylene block polymers, polyethylene glycol, and antioxidants (including ascorbic acid and methionine); preservatives; low molecular weight (less than about 10 residues) peptides; proteins; and amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine. In advantageous embodiments, the excipient may be one or more selected from the list consisting of NaCl, trehalose, sucrose, mannitol, or glycine.

[0486] This disclosure also covers products that can be obtained by further processing liquid formulations, such as products obtained by freezing, lyophilization, or spray drying. Upon reconfiguration, these solid products can become liquid formulations as described herein (but are not limited to). Therefore, in its broadest sense, the term "formulation" encompasses both liquid and solid formulations. However, solid formulations are understood to be derived from liquid formulations (e.g., by freezing, lyophilization, or spray drying) and thus possess a variety of characteristics defined by the characteristics of liquid formulations specified herein.

[0487] In some embodiments, the preparation is isotonic with human blood. An isotonic solution has the same osmotic pressure as plasma, and therefore can be intravenously infused into the subject without altering the plasma's osmotic pressure.

[0488] In some embodiments, considering that attenuated RSV, recombinant vectors and nucleic acids, viral particles and peptides can be stored as unit dosage forms, the prepared titers are approximately 10 mM Tris and 140 mM NaCl (pH 7.7). To prepare the vaccine injection, for example, 10... 2 -10 8 Or 10 2 -10 9 Virus particles or virus-like particles are lyophilized in phosphate-buffered saline (PBS) in a sealed container (preferably a glass ampoule) in the presence of peptone and human albumin. Alternatively, the vaccine injection can be produced by stepwise freeze-drying of a formulation. This formulation may contain additional additives (e.g., mannitol, dextran, sugar, glycine, lactose, or polyvinylpyrrolidone) or other adjuvants suitable for in vivo administration (e.g., antioxidants or inert gases, stabilizers, or recombinant proteins (e.g., human serum albumin)). For vaccination or therapy, the lyophilized material can be dissolved in an aqueous solution (preferably physiological saline or tris(hydroxymethyl)aminomethane buffer). In some embodiments, the vaccine or pharmaceutical composition is administered intranasally or intramuscularly.

[0489] In some embodiments, the vaccine or pharmaceutical composition is administered systemically or locally (i.e., parenteral, subcutaneous, intravenous, intramuscular, intranasal, or any other route of administration). The method of administration, dosage, and frequency of administration can be optimized.

[0490] In some embodiments, this disclosure relates to a kit containing materials that can be used for vaccination, treatment, or prevention of RSV infection as described above. In some embodiments, the kit includes a container, product label, and instructions for use. Suitable containers include, for example, bottles, vials, syringes, and boxes containing them. Containers can be made of a variety of materials, such as glass, plastic, or cardboard. The container contains a composition that effectively treats the condition and may have a sterile access port (e.g., the container may be an intravenous solution bag or a vial with a stopper that can be punctured by a hypodermal needle). At least one active agent in the composition is a peptide, viral particle / virus-like particle, nucleic acid, vector, or attenuated virus as disclosed herein. The product label on or attached to the container indicates that the composition is intended to treat the selected condition. In some embodiments, the kit may further include a second container containing a pharmaceutically acceptable buffer, such as phosphate-buffered saline or citrate-buffered saline. It may further include other materials desired from a user or commercial perspective, including additional buffers, diluents, filters, needles, and syringes. In some embodiments, the dosage unit may be in the form of, for example, a pre-filled syringe, ampoule, cartridge, or vial.

[0491] In some embodiments, this disclosure relates to kits or articles of manufacture that comprise peptides, viral particles, nucleic acids, vectors, or attenuated viral formulations thereof as disclosed herein, along with instructions for use by, for example, healthcare professionals. Kits or articles of manufacture may include containers, vials, or syringes containing formulations as described herein.

[0492] Preferably, the container, vial, or syringe is made of glass, plastic, or a polymeric material selected from cyclic olefin polymers or copolymers. The syringe, ampoule, cartridge, or vial can be made of any suitable material (e.g., glass or plastic) and may include rubber materials, such as rubber stoppers for vials and rubber plungers and seals for syringes and cartridges. In some embodiments, the kit may further include instructions for use and / or clinical drug instructions. In any embodiment of the product as defined herein, this disclosure also covers the presence of packaging materials, instructions for use, and / or clinical drug instructions (e.g., as required by regulatory authorities).

[0493] RSV platform for VLPs of G, F, or G plus F proteins

[0494] The RSV VLP platforms M+P and M+M2-1, with F and G, F and G peptides, or truncated F and G on their surfaces, were considered. Immunoblotting of sucrose gradient purified particles revealed co-expression of M, G, and F with both VLP platforms. Electron microscopy imaging and immunogold labeling confirmed the VLP-like structures, with exposed protrusions on their surfaces consistent with F and G proteins. In mice, VLPs induced anti-F and anti-G protein antibodies and reduced viral titers and inflammation in the lungs after challenge, suggesting that these RSV VLP platforms provide a tool for studying the structure and interactions of F and G, as well as a flexible platform for developing VLP vaccines in which all components contribute to an RSV-specific immune response. See Ha et al., Viruses [Virus] 2020, 12, 906, 1-17.

[0495] RSV is a single-stranded negative-sense RNA virus. The RSV genome (approximately 15.2 kb) comprises 10 genes encoding 11 proteins. Glycoproteins, fusion proteins (F), attachment proteins (G), and small hydrophobic proteins (SH) are expressed on the viral envelope. The F and G proteins induce potent neutralizing antibodies and protective immunity. Most neutralizing antibodies in human serum target the pre-fusion form of F. The G protein typically elicits weaker neutralizing antibodies. Structurally, the G protein consists of a conserved region containing a CX3C chemokine motif that enables it to bind to the CX3C chemokine receptor CX3CR1. Experiments in BALB / c mice have shown that G induces disease with inflammatory responses that can be blocked by passive administration of anti-G monoclonal antibodies, G peptide vaccine-induced antibody inhibition of G-CX3CR1 binding, or by mutation of the CX3C motif. G-CX3CR1 binding mediates infection of primary human respiratory epithelial cells. The interaction between F and G was demonstrated by the following: immunoprecipitation assays, cryo-electron tomography (cryo-ET) studies of the effect of G on F in viral particles, and the induction of lung mucus in mice by both F and G requiring mutations.

[0496] This article reports RSV VLPs incorporating F and / or RSV M and P or M and M2-1. In addition to VLPs containing M and P, VLPs containing M and M2-1 were also considered. RSV VLPs expressing F and G on the surface, F and G peptides, and F and G without most of their extracellular domains were generated, and their ability to protect against RSV attack was demonstrated.

[0497] Cells, culture medium, and plasmids:

[0498] Cells (293F) were stably transfected with plasmid pcDNA6 / TR and incubated on a freestyle oscillator at 37°C and 8% CO2. TMCultured in 293 medium. DNA plasmids (pcDNA3.1) containing codon-optimized RSV genes M, M2-1, P, G, and F from the A2 strain were used. The plasmids were digested with KpnI and XhOI enzymes and cloned into KpnI and XhOI-double-digested pcDNA4 / TO or pcDNA5 / TO vectors. See Ha et al. Viruses [viruses]. 2020, 12(9): 906.

[0499] A truncated G, optimized with human codons and consisting of amino acids 1-86 plus 155-206, was synthesized. The gene provided in the pUC57 plasmid was digested with BamHI and XhOI restriction endonucleases and cloned into the BamHI and XhOI-digested pcDNA5 / TO vector. Sequence confirmation of all genes was performed prior to transfection. To generate VLPs, 293F cells were sequentially and stably transfected with RSV genes, specifically by stably transfecting 293F cells with genes expressing M, M2-1, and pF, followed by stably transfecting with genes expressing different versions of Ga and / or Gb.

[0500] Virus-like particle expression and purification: a total of 20-30 × 10⁻⁶ particles were expressed and purified. 6 293F cells were induced with 2 μg / mL doxycycline for 72 h. Cells were centrifuged at 300 × g for 10 min, and the medium containing VLP was filtered through a 0.45 μm filter, followed by centrifugation at 12,200 × g for 2 h at 4°C via a 20% sucrose pad. The top layer of cell culture medium and sucrose was thoroughly removed, and the pellet was incubated on ice with sterile PBS for 1 h and resuspended. For the sucrose gradient assay, a linear sucrose gradient was prepared. 1 mL of the gradient was taken, and the resuspended VLP was plated onto the gradient and centrifuged at 11,000 × g for 12 h at 4°C. Ten 1-mL fractions were removed from the top, diluted 3-fold with sterile PBS, and centrifuged at 12,000 × g for 1 h at 4°C on a benchtop centrifuge. The supernatant was removed, and the pellet was incubated on ice with sterile PBS for 1 h and resuspended.

[0501] F, Ga and Gb ELISA:

[0502] Secretory forms of F, Ga, or Gb protein antigens were produced from 293F cells stably transfected in serum-free medium and coated onto 96-well microtiter plates with coating buffer (15 mM Na₂CO₃, 35 mM NaHCO₃, 3 mM NaN₃, pH 9.4–9.6). The plates were incubated at 37°C for 2 h in 2% skim milk powder dissolved in PBS blocking solution, washed with PBS-T (PBS with 0.15% Tween-20), and serum samples diluted 1:200 were added to the wells. The plates were incubated at 37°C for 1 h, washed with PBS-T, and goat anti-mouse IgG-HRP (1:5000) was added and incubated at 37°C for 1 h. Color development was performed using o-phenylenediamine dihydrochloride (OPD) substrate, and the reaction was stopped with 4N H₂SO₄ after 30 min at room temperature. The absorbance was measured at an optical density (OD) of 490 nm using a microplate reader, and the geometric mean of OD490 was calculated from three copies of the wells.

[0503] Generation of G and F virus-like particles (VLPs) on RSV M and P or M and M2-1 platforms

[0504] RSV VLPs were generated by transfecting 293F cells with a DNA plasmid sequence optimized with codons containing the RSV gene. Western blot analysis showed that VLPs containing F or F and G were successfully developed using the RSV M+P or M+M2-1 protein platform, but at very low levels when only G was present, whereas F was not observed in VLPs expressing only F. This meant that F or F and G were detected in the supernatant of induced 293F cells, but not in the cell pellet. The VLPs were released from the cells. Furthermore, after centrifugation via a sucrose pad, F or F and G were detected in the pellet by Western blot, indicating that the protein was incorporated into the pellet but not in solution in the culture medium. Finally, after sucrose gradient purification, F and M, or F, G, and M, were detected in the same fraction by Western blot, indicating the presence of M in VLPs containing F and F and G.

[0505] F and G peptides were co-expressed with the first 20 amino acids (amino acids 1-86) of the intracellular, transmembrane, and extracellular domains, plus amino acids 155-206 representing the central conserved domain (GP). As shown in Western blot studies of VLPs purified via a sucrose gradient, VLPs with either an M+P or M+M2-1 platform were generated. G alone was inefficient, but it was efficiently incorporated into VLPs when combined with F, indicating that F promotes the generation of G VLPs. Truncated F (Ft) (retaining the carboxyl terminus, the transmembrane region, and the first 26 amino acids of the extracellular domain) were generated for co-expression with full-length G. Ft and G were highly expressed in VLPs (using M+P VLPs).

[0506] Animal research

[0507] Female BALB / c mice aged four to six weeks were immunized by intramuscular injection of 50 μg VLP on day 1 (primary immunization) and day 21 (booster immunization). Mice were euthanized on day 42, and serum was separated and stored at -80°C until use.

Claims

1. A recombinant RSV G protein, said recombinant RSV G protein comprising R15K, G29C, M48I, I49V, N81S, T87P and R197K mutations.

2. The recombinant RSV G protein of claim 1, wherein the recombinant RSV G protein comprises the following amino acid sequence: MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIV (SEQ ID NO: 27).

3. The recombinant RSV G protein of claim 1, wherein the recombinant RSV G protein comprises the following amino acid sequence: MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNT (SEQ ID NO: 17, Ga 1-86).

4. The recombinant RSV G protein of claim 1, wherein the recombinant RSV G protein comprises the following amino acid sequence: MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANKVTPTTAIIQDATSQIKNTPP (SEQ ID NO: 18, Ga 1-86 C-terminal PP), or MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTTPTYLTQNPQLGISPSNPSE (SEQ ID NO: 35, Ga 1-106).

5. The recombinant RSV G protein of claim 1, wherein the recombinant RSV G protein comprises the following amino acid sequence: PSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 19, Ga 155-206), or TPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 37, Gb 150-210).

6. The recombinant RSV G protein of claim 1, wherein the recombinant RSV G protein comprises the following amino acid sequence: MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 1, Ga 1-86 plus 155-206 (Ga)).

7. The recombinant RSV G protein of claim 1, wherein the recombinant RSV G protein comprises the following amino acid sequence: MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTQRQNKPPSKPNNDFHFEVVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTLKTPRLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 5, group A 1-86 plus 150-210 plus group B 150-210, series Ga plus Gb (T-Ga / Gb)).

8. The recombinant RSV G protein of claim 1, wherein the recombinant RSV G protein comprises the following amino acid sequence: KPTLKTPRL (SEQ ID NO: 21, linker Gb).

9. The recombinant RSV G protein of claim 1, wherein the recombinant RSV G protein comprises the following amino acid sequence: QRQNKPPSKPNNDFHFFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTPLKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPSNKPKKKPTIKPTNKPTTKT (SEQ ID NO: 20, Gb 150-210).

10. The recombinant RSV G protein of claim 1, wherein the recombinant RSV G protein comprises the following amino acid sequence: MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAIACKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 9, Ga CX4C 1-86 plus 145-206).

11. The recombinant RSV G protein of claim 1, wherein the recombinant RSV G protein comprises the following amino acid sequence: KPTTKQRQNK (SEQ ID NO: 28, Ga 145-154).

12. The recombinant RSV G protein of claim 1, wherein the recombinant RSV G protein comprises the following amino acid sequence: CWAIAC (SEQ ID NO: 22, Ga CX4C).

13. The recombinant RSV G protein of claim 1, wherein the recombinant RSV G protein comprises the following amino acid sequence: MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFFEVFNFVPCSICRNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 11, Ga 1-86 plus 145-206 S177R) or MSKNKDQRTAKTLERTWDTLNHLLFISSCLYKLNLKSVAQITLSILAIVISTSLIIAAIIFIASANHKVTPTTAIIQDATSQIKNTKPTTKQRQNKPPSKPNNDFHFEVVFNFVPCSICQNNPTCWAICKRIPNKKPGKKTTTKPTKKP (SEQ ID NO: 13, Ga 1-86 plus 145-206 S177Q).

14. The recombinant RSV G protein of claim 1, wherein the recombinant RSV G protein comprises S177R and / or S177Q mutations.

15. A virus-like particle comprising the recombinant RSV G protein as claimed in any one of claims 1-14.

16. A nucleic acid encoding a recombinant RSV G protein as described in any one of claims 1-14, wherein the nucleic acid is operatively combinable with a heterologous promoter.

17. The nucleic acid of claim 16, wherein the nucleic acid is RNA or DNA.

18. A live attenuated RSV strain, said live attenuated RSV strain comprising the recombinant RSV G protein as described in any one of claims 1-14.

19. A vector comprising the nucleic acid as described in claim 16 or encoding the recombinant RSV G protein as described in any one of claims 1-14.

20. A method of vaccinating against or treating RSV infection, the method comprising administering an effective amount of a vaccine or pharmaceutical composition to a subject in need, said vaccine or pharmaceutical composition comprising a recombinant RSV G protein, virus-like particles, virus particles, nucleic acid, attenuated RSV strain, attenuated RSV virus, or vector as described in any one of claims 1-19.

21. A vaccine or pharmaceutical composition comprising, as described in any one of claims 1-19, a recombinant RSV G protein, virus-like particles, virus particles, nucleic acid, an attenuated RSV strain, an attenuated RSV virus, or a vector.

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