Single-dose avian influenza A(H5N1) Clade 2.3.4.4b hemagglutinin–Matrix-M® nanoparticle vaccine induces neutralizing responses in nonhuman primates
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Abstract
ABSTRACT With the recent rise in cases of highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b infection in humans and animals, there is an associated increase in the risk of human-to-human transmission. In this study, we characterize recombinant A(H5N1) A/American Wigeon/South Carolina/22/000345-001/2021 (A/AW/SC/2021) clade 2.3.4.4b vaccine. Purified recombinant A/AW/SC/2021 HA trimers upon formulation with Matrix-M™ adjuvant, saponin-cholesterol-phospholipid icosahedral particles, non-covalently anchored to the vertices of the Matrix-M forming A(H5N1) HA – Matrix-M nanoparticles (H5-MNPs). In naïve mice, two intranasal (IN) or intramuscular (IM) doses of A/AW/SC/2021 H5-MNP vaccine induced robust antibody- and cell-mediated immune responses, including neutralizing antibodies against A(H5N1). In non-human primates (NHPs) primed with seasonal influenza vaccine, a single IM or IN dose of the A/AW/SC/2021 H5-MNP vaccine induced geometric mean serum A(H5N1) clade 2.3.4.4b pseudovirus neutralizing titers of 1:1160 and 1:54, respectively; above the generally accepted seroconverting neutralizing titer of 1:40. Immunization with H5-MNP vaccine induced antibody responses against conserved epitopes in the A(H5N1) HA stem, vestigial esterase subdomain, and receptor binding site. This novel A(H5N1) H5-MNP IN and IM vaccine was immunogenic in rodents and NHPs as a potential A(H5N1) pandemic single-dose vaccine.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Furey, C., Scher, G., Ye, N., Kercher, L., DeBeauchamp, J., Crumpton, J. C., Jeevan, T., Patton, C., Franks, J., Rubrum, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48555-z · Cited by 79 · see citing works
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- Authors
- Patel, N., Rehman, A., Trost, J. F., Flores, R., Longacre, Z., Guebre-Xabier, M., Zhou, H., Zhou, B., Jacobson, K., Jiang, D., Bai, X., Khatoon, R., Kort, T., Norton, J., Madhangi, M., Hersey, M., Greene, A. M., Dubovsky, F., & Smith, G.
- Affiliations
- Novavax (United States) (US)
- Corresponding author
- Smith, Gale
- ORCID
- Venue
- Nature Communications
- Published
- 2025-07-18
- Volume
- 16
- Issue
- 1
- Pages
- 6625-6625
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC12274490
- OpenAlex
- W4412520772
- Cited by
- 6
- References
- 2
- Citations by year
- 2026: 4 · 2025: 2
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Novavax, Inc.
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- H5N1 avian influenza, clade 2.3.4.4b, hemagglutinin, nanoparticle vaccine, Matrix-M adjuvant, neutralizing antibodies, non-human primates, single-dose vaccine, intranasal immunization, cell-mediated immunity, receptor binding sites, pandemic influenza preparedness, human-to-human transmission
- MeSH terms
- Nanovaccines, Administration, Intranasal, Animals, Antibodies, Viral, Female, Humans, Influenza Vaccines, Injections, Intramuscular, Mice, Inbred BALB C, Orthomyxoviridae Infections, Hemagglutinin Glycoproteins, Influenza Virus, Mice, Influenza A Virus, H5N1 Subtype, Nanoparticles, Antibodies, Neutralizing
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