PreprintCited by 6Influenza Virus Research StudiesVirology and Viral DiseasesBacterial Infections and Vaccines

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

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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Preprint — published as 10.1038/s41467-025-61964-y · Paper page

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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Metadata

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
Venue
Nature Communications
Publisher
openRxiv
Published
2024-11-21
Volume
16
Issue
1
Pages
6625-6625
ISSN
2041-1723 (ISSN-L)
OpenAlex
W4412520772
Cited by
6
References
1
Citations by year
2026: 4 · 2025: 2
FWCI
4.16
Type
journal article
Language
en
Open access
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
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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