Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus.
Animals
Influenza Vaccines
/ immunology
Female
Mice
Ferrets
Nanoparticles
/ chemistry
Male
Influenza A Virus, H5N1 Subtype
/ immunology
Antibodies, Viral
/ immunology
Hemagglutinin Glycoproteins, Influenza Virus
/ immunology
Orthomyxoviridae Infections
/ prevention & control
mRNA Vaccines
/ immunology
Antibodies, Neutralizing
/ immunology
Mice, Inbred BALB C
Influenza in Birds
/ prevention & control
Humans
RNA, Messenger
/ genetics
Influenza A Virus, H1N1 Subtype
/ immunology
Birds
/ virology
Lipids
/ chemistry
Liposomes
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 May 2024
23 May 2024
Historique:
received:
04
05
2023
accepted:
06
05
2024
medline:
24
5
2024
pubmed:
24
5
2024
entrez:
23
5
2024
Statut:
epublish
Résumé
mRNA lipid nanoparticle (LNP) vaccines would be useful during an influenza virus pandemic since they can be produced rapidly and do not require the generation of egg-adapted vaccine seed stocks. Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating at unprecedently high levels in wild and domestic birds and have the potential to adapt to humans. Here, we generate an mRNA lipid nanoparticle (LNP) vaccine encoding the hemagglutinin (HA) glycoprotein from a clade 2.3.4.4b H5 isolate. The H5 mRNA-LNP vaccine elicits strong T cell and antibody responses in female mice, including neutralizing antibodies and broadly-reactive anti-HA stalk antibodies. The H5 mRNA-LNP vaccine elicits antibodies at similar levels compared to whole inactivated vaccines in female mice with and without prior H1N1 exposures. Finally, we find that the H5 mRNA-LNP vaccine is immunogenic in male ferrets and prevents morbidity and mortality of animals following 2.3.4.4b H5N1 challenge. Together, our data demonstrate that a monovalent mRNA-LNP vaccine expressing 2.3.4.4b H5 is immunogenic and protective in pre-clinical animal models.
Identifiants
pubmed: 38782954
doi: 10.1038/s41467-024-48555-z
pii: 10.1038/s41467-024-48555-z
doi:
Substances chimiques
Influenza Vaccines
0
Antibodies, Viral
0
Hemagglutinin Glycoproteins, Influenza Virus
0
Lipid Nanoparticles
0
mRNA Vaccines
0
Antibodies, Neutralizing
0
RNA, Messenger
0
Lipids
0
Liposomes
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4350Subventions
Organisme : NIAID NIH HHS
ID : 75N93021C00015
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93021C00016
Pays : United States
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01AI08686
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01AI126899
Informations de copyright
© 2024. The Author(s).
Références
Group, W. O. F. H. N. E. W. Continued evolution of highly pathogenic avian influenza A (H5N1): updated nomenclature. Influenza Other Respiratory Viruses 6, 1–5 (2012).
doi: 10.1111/j.1750-2659.2011.00298.x
Lewis, N. S. et al. Emergence and spread of novel H5N8, H5N5 and H5N1 clade 2.3.4.4 highly pathogenic avian influenza in 2020. Emerg. Microbes Infect. 10, 148–151 (2021).
doi: 10.1080/22221751.2021.1872355
pubmed: 33400615
pmcid: 7832535
Verhagen, J. H., Fouchier, R. A. M. & Lewis, N. Highly pathogenic avian influenza viruses at the wild–domestic bird interface in Europe: future directions for research and surveillance. Viruses 13, 212 (2021).
doi: 10.3390/v13020212
pubmed: 33573231
pmcid: 7912471
Global Consortium for, H. N. & Related Influenza Viruses. Role for migratory wild birds in the global spread of avian influenza H5N8. Science 354, 213–217 (2016).
Lycett, S. J. et al. Genesis and spread of multiple reassortants during the 2016/2017 H5 avian influenza epidemic in Eurasia. Proc. Natl Acad. Sci. USA 117, 20814–20825 (2020).
doi: 10.1073/pnas.2001813117
pubmed: 32769208
pmcid: 7456104
Caliendo, V. et al. Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021. Sci. Rep. 12, 11729 (2022).
doi: 10.1038/s41598-022-13447-z
pubmed: 35821511
pmcid: 9276711
King, J. et al. Highly pathogenic avian influenza virus incursions of subtype H5N8, H5N5, H5N1, H5N4, and H5N3 in Germany during 2020-21. Virus Evol. 8, veac035 (2022).
doi: 10.1093/ve/veac035
pubmed: 35478715
pmcid: 9037367
Adlhoch, C. et al. Avian influenza overview December 2022 - March 2023. EFSA J. 21, e07917 (2023).
pubmed: 36949860
pmcid: 10025949
Authority, E. F. S. et al. Avian influenza overview May – September 2021. EFSA J. 20, e07122 (2022).
High pathogenicity avian influenza (HPAI)- situation report, 12 February 2022. (World Organisation for Animal Health-World Animal Health Information System, 2022).
European Food Safety, A. et al. Avian influenza overview March - June 2022. EFSA J. 20, e07415 (2022).
FAO-UN. Global Avian Influenza Viruses with Zoonotic Potential situation update, 25 April 2024 https://www.fao.org/animal-health/situation-updates/ (2024).
Bordes, L. et al. Highly pathogenic avian influenza H5N1 virus infections in wild red foxes (Vulpes vulpes) show neurotropism and adaptive virus mutations. Microbiol Spectr. 11, e02867–02822 (2023).
doi: 10.1128/spectrum.02867-22
pubmed: 36688676
pmcid: 9927208
Rijks, J. M. et al. Highly pathogenic avian influenza A(H5N1) virus in wild red foxes, the Netherlands, 2021. Emerg. Infect. Dis. 27, 2960–2962 (2021).
doi: 10.3201/eid2711.211281
pubmed: 34670656
pmcid: 8544991
Puryear, W. et al. Highly Pathogenic Avian Influenza A(H5N1) virus outbreak in New England Seals, United States. Emerg. Infect. Dis. 29, 786–791 (2023).
Pyankova, O. G. et al. Isolation of clade 2.3.4.4b A(H5N8), a highly pathogenic avian influenza virus, from a worker during an outbreak on a poultry farm, Russia, December 2020. Euro. Surveill. 26, 2100439 (2021).
doi: 10.2807/1560-7917.ES.2021.26.24.2100439
pubmed: 34142650
pmcid: 8212591
Agüero, M. et al. Highly pathogenic avian influenza A(H5N1) virus infection in farmed minks, Spain, October 2022. Euro. Surveill. 28, 2300001 (2023).
doi: 10.2807/1560-7917.ES.2023.28.3.2300001
pubmed: 36695488
pmcid: 9853945
Floyd, T. et al. Encephalitis and death in wild mammals at a rehabilitation center after infection with highly pathogenic avian influenza A(H5N8) virus, United Kingdom. Emerg. Infect. Dis. 27, 2856 (2021).
doi: 10.3201/eid2711.211225
pubmed: 34670647
pmcid: 8544989
Postel, A. et al. Infections with highly pathogenic avian influenza A virus (HPAIV) H5N8 in harbor seals at the German North Sea coast, 2021. Emerg. Microbes Infect. 11, 725–729 (2022).
doi: 10.1080/22221751.2022.2043726
pubmed: 35172704
pmcid: 8890524
Alkie, T. N. et al. Characterization of neurotropic HPAI H5N1 viruses with novel genome constellations and mammalian adaptive mutations in free-living mesocarnivores in Canada. Emerg. Microbes Infect. 12, 2186608 (2023).
doi: 10.1080/22221751.2023.2186608
pubmed: 36880345
pmcid: 10026807
Feldman, R. A. et al. mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Vaccine 37, 3326–3334 (2019).
doi: 10.1016/j.vaccine.2019.04.074
pubmed: 31079849
Pardi, N. et al. Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies. Nat. Commun. 9, 3361 (2018).
doi: 10.1038/s41467-018-05482-0
pubmed: 30135514
pmcid: 6105651
Willis, E. et al. Nucleoside-modified mRNA vaccination partially overcomes maternal antibody inhibition of de novo immune responses in mice. Sci. Transl. Med. 12, eaav5701 (2020).
doi: 10.1126/scitranslmed.aav5701
pubmed: 31915303
pmcid: 7339908
Arevalo, C. P. et al. A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Science 378, 899–904 (2022).
doi: 10.1126/science.abm0271
pubmed: 36423275
pmcid: 10790309
Freyn, A. W. et al. A multi-targeting, nucleoside-modified mRNA influenza virus vaccine provides broad protection in mice. Mol. Ther. 28, 1569–1584 (2020).
doi: 10.1016/j.ymthe.2020.04.018
pubmed: 32359470
pmcid: 7335735
Topol, E. J. Messenger RNA vaccines against SARS-CoV-2. Cell 184, 1401 (2021).
doi: 10.1016/j.cell.2020.12.039
pubmed: 33740443
pmcid: 7805392
Kandeil, A. et al. Rapid evolution of A(H5N1) influenza viruses after intercontinental spread to North America. Nat. Commun. 14, 3082 (2023).
doi: 10.1038/s41467-023-38415-7
pubmed: 37248261
pmcid: 10227026
Neuzil, K. M. et al. Safety and immunogenicity of influenza A/H5N8 virus vaccine in healthy adults: durability and cross-reactivity of antibody responses. Clin. Infect. Dis. https://doi.org/10.1093/cid/ciac982 (2023).
Li, H. et al. Recombinant parainfluenza virus 5 expressing clade 2.3.4.4b H5 hemagglutinin protein confers broad protection against H5Ny influenza viruses. J. Virol. 98, e0112923 (2024).
doi: 10.1128/jvi.01129-23
pubmed: 38305155
Rudometova, N. B. et al. Immunogenic and protective properties of recombinant hemagglutinin of influenza A (H5N8) virus. Vaccines 12, 143 (2024).
doi: 10.3390/vaccines12020143
pubmed: 38400127
pmcid: 10893068
Farley, M. M. 2009 H1N1 influenza: a twenty-first century pandemic with roots in the early twentieth century. Am. J. Med. Sci. 340, 202–208, (2010).
doi: 10.1097/MAJ.0b013e3181e937b0
pubmed: 20697263
pmcid: 7119454
Pardi, N., Muramatsu, H., Weissman, D. & Kariko, K. In vitro transcription of long RNA containing modified nucleosides. Methods Mol. Biol. 969, 29–42 (2013).
doi: 10.1007/978-1-62703-260-5_2
pubmed: 23296925
Baiersdorfer, M. et al. A facile method for the removal of dsRNA contaminant from in vitro-transcribed mRNA. Mol. Ther. Nucleic Acids 15, 26–35 (2019).
doi: 10.1016/j.omtn.2019.02.018
pubmed: 30933724
pmcid: 6444222
Maier, M. A. et al. Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics. Mol. Ther. 21, 1570–1578 (2013).
doi: 10.1038/mt.2013.124
pubmed: 23799535
pmcid: 3734658
Linderman, S. L. et al. Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013-2014 influenza season. Proc. Natl. Acad. Sci. USA 111, 15798–15803 (2014).
doi: 10.1073/pnas.1409171111
pubmed: 25331901
pmcid: 4226110
Whittle, J. R. et al. Flow cytometry reveals that H5N1 vaccination elicits cross-reactive stem-directed antibodies from multiple Ig heavy-chain lineages. J. Virol. 88, 4047–4057 (2014).
doi: 10.1128/JVI.03422-13
pubmed: 24501410
pmcid: 3993745
Doud, M. B., Hensley, S. E. & Bloom, J. D. Complete mapping of viral escape from neutralizing antibodies. PLOS Pathog. 13, e1006271 (2017).
doi: 10.1371/journal.ppat.1006271
pubmed: 28288189
pmcid: 5363992
Gouma, S. et al. Middle-aged individuals may be in a perpetual state of H3N2 influenza virus susceptibility. Nat. Commun. 11, 4566 (2020).
doi: 10.1038/s41467-020-18465-x
pubmed: 32917903
pmcid: 7486384
Monaco, G. et al. flowAI: automatic and interactive anomaly discerning tools for flow cytometry data. Bioinformatics 32, 2473–2480 (2016).
doi: 10.1093/bioinformatics/btw191
pubmed: 27153628
Reed, L. J. & Muench, H. A simple method of estimating fifty percent endpoints. Am. J. Epidemiol. 27, 493–497 (1938).
doi: 10.1093/oxfordjournals.aje.a118408