Development of a Nucleoside-modified MRNA Vaccine Against Clade 2.3.4.4b H5 Highly Pathogenic Avian Influenza Virus

Overview

Journal Nat Commun

Specialty Biology

Date 2024 May 23

PMID 38782954

Authors

Colleen Furey

Gabrielle Scher

Naiqing Ye

Lisa Kercher

Jennifer DeBeauchamp

Jeri Carol Crumpton

Trushar Jeevan

Christopher Patton

John Franks

Adam Rubrum

Mohamad-Gabriel Alameh

Steven H Y Fan

Anthony T Phan

Christopher A Hunter

Richard J Webby

Drew Weissman

Scott E Hensley

Affiliations

Soon will be listed here.

Abstract

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.

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References

Pyankova O, Susloparov I, Moiseeva A, Kolosova N, Onkhonova G, Danilenko A . 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. 2021; 26(24). PMC: 8212591. DOI: 10.2807/1560-7917.ES.2021.26.24.2100439. View

Lewis N, Banyard A, Whittard E, Karibayev T, Al Kafagi T, Chvala I . Emergence and spread of novel H5N8, H5N5 and H5N1 clade 2.3.4.4 highly pathogenic avian influenza in 2020. Emerg Microbes Infect. 2021; 10(1):148-151. PMC: 7832535. DOI: 10.1080/22221751.2021.1872355. View

. Continued evolution of highly pathogenic avian influenza A (H5N1): updated nomenclature. Influenza Other Respir Viruses. 2011; 6(1):1-5. PMC: 5074649. DOI: 10.1111/j.1750-2659.2011.00298.x. View

Baiersdorfer M, Boros G, Muramatsu H, Mahiny A, Vlatkovic I, Sahin U . A Facile Method for the Removal of dsRNA Contaminant from In Vitro-Transcribed mRNA. Mol Ther Nucleic Acids. 2019; 15:26-35. PMC: 6444222. DOI: 10.1016/j.omtn.2019.02.018. View

Adlhoch C, Fusaro A, Gonzales J, Kuiken T, Marangon S, Niqueux E . Avian influenza overview March - June 2022. EFSA J. 2022; 20(8):e07415. PMC: 9356771. DOI: 10.2903/j.efsa.2022.7415. View

Feldman R, Fuhr R, Smolenov I, Ribeiro A, Panther L, Watson M . 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. 2019; 37(25):3326-3334. DOI: 10.1016/j.vaccine.2019.04.074. View

Verhagen J, Fouchier R, Lewis N . Highly Pathogenic Avian Influenza Viruses at the Wild-Domestic Bird Interface in Europe: Future Directions for Research and Surveillance. Viruses. 2021; 13(2). PMC: 7912471. DOI: 10.3390/v13020212. View

King J, Harder T, Globig A, Stacker L, Gunther A, Grund C . Highly pathogenic avian influenza virus incursions of subtype H5N8, H5N5, H5N1, H5N4, and H5N3 in Germany during 2020-21. Virus Evol. 2022; 8(1):veac035. PMC: 9037367. DOI: 10.1093/ve/veac035. View

Alkie T, Cox S, Embury-Hyatt C, Stevens B, Pople N, Pybus M . Characterization of neurotropic HPAI H5N1 viruses with novel genome constellations and mammalian adaptive mutations in free-living mesocarnivores in Canada. Emerg Microbes Infect. 2023; 12(1):2186608. PMC: 10026807. DOI: 10.1080/22221751.2023.2186608. View

10.

Rijks J, Hesselink H, Lollinga P, Wesselman R, Prins P, Weesendorp E . Highly Pathogenic Avian Influenza A(H5N1) Virus in Wild Red Foxes, the Netherlands, 2021. Emerg Infect Dis. 2021; 27(11):2960-2962. PMC: 8544991. DOI: 10.3201/eid2711.211281. View

11.

Adlhoch C, Fusaro A, Gonzales J, Kuiken T, Marangon S, Mirinaviciute G . Avian influenza overview December 2022 - March 2023. EFSA J. 2023; 21(3):e07917. PMC: 10025949. DOI: 10.2903/j.efsa.2023.7917. View

12.

Doud M, Hensley S, Bloom J . Complete mapping of viral escape from neutralizing antibodies. PLoS Pathog. 2017; 13(3):e1006271. PMC: 5363992. DOI: 10.1371/journal.ppat.1006271. View

13.

Rudometova N, Fando A, Kisakova L, Kisakov D, Borgoyakova M, Litvinova V . Immunogenic and Protective Properties of Recombinant Hemagglutinin of Influenza A (H5N8) Virus. Vaccines (Basel). 2024; 12(2). PMC: 10893068. DOI: 10.3390/vaccines12020143. View

14.

Monaco G, Chen H, Poidinger M, Chen J, de Magalhaes J, Larbi A . flowAI: automatic and interactive anomaly discerning tools for flow cytometry data. Bioinformatics. 2016; 32(16):2473-80. DOI: 10.1093/bioinformatics/btw191. View

15.

Postel A, King J, Kaiser F, Kennedy J, Lombardo M, Reineking W . Infections with highly pathogenic avian influenza A virus (HPAIV) H5N8 in harbor seals at the German North Sea coast, 2021. Emerg Microbes Infect. 2022; 11(1):725-729. PMC: 8890524. DOI: 10.1080/22221751.2022.2043726. View

16.

Floyd T, Banyard A, Lean F, Byrne A, Fullick E, Whittard E . 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. 2021; 27(11):2856-2863. PMC: 8544989. DOI: 10.3201/eid2711.211225. View

17.

Li H, Sun H, Tao M, Han Q, Yu H, Li J . Recombinant parainfluenza virus 5 expressing clade 2.3.4.4b H5 hemagglutinin protein confers broad protection against H5Ny influenza viruses. J Virol. 2024; 98(3):e0112923. PMC: 10949453. DOI: 10.1128/jvi.01129-23. View

18.

Whittle J, Wheatley A, Wu L, Lingwood D, Kanekiyo M, Ma S . Flow cytometry reveals that H5N1 vaccination elicits cross-reactive stem-directed antibodies from multiple Ig heavy-chain lineages. J Virol. 2014; 88(8):4047-57. PMC: 3993745. DOI: 10.1128/JVI.03422-13. View

19.

Puryear W, Sawatzki K, Hill N, Foss A, Stone J, Doughty L . Highly Pathogenic Avian Influenza A(H5N1) Virus Outbreak in New England Seals, United States. Emerg Infect Dis. 2023; 29(4):786-791. PMC: 10045683. DOI: 10.3201/eid2904.221538. View

20.

Arevalo C, Bolton M, Le Sage V, Ye N, Furey C, Muramatsu H . A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Science. 2022; 378(6622):899-904. PMC: 10790309. DOI: 10.1126/science.abm0271. View