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TitleSingle-dose avian influenza A(H5N1) Clade 2.3.4.4b hemagglutinin-Matrix-M nanoparticle vaccine induces neutralizing responses in nonhuman primates.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 6625, Year 2025
Publish dateJul 18, 2025
AuthorsNita Patel / Asma Rehman / Jessica F Trost / Rhonda Flores / Zach Longacre / Mimi Guebre-Xabier / Haixia Zhou / Bin Zhou / Kelsey Jacobson / Desheng Jiang / Xiaoyun Bai / Rafia Khatoon / Thomas Kort / James Norton / M Madhangi / Melinda Hersey / Ann M Greene / Filip Dubovsky / Gale Smith /
PubMed AbstractWith 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 ...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 a 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 formulated with Matrix-M adjuvant, saponin-cholesterol-phospholipid combination arranged in cage-like particles, are found to non-covalently anchor to the vertices of the Matrix-M and form A(H5N1) HA-Matrix-M nanoparticles (H5-MNPs). In naïve female mice, two intranasal (IN) or intramuscular (IM) doses of A/AW/SC/2021 H5-MNP vaccine induces 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 induces 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 induces antibody responses against conserved epitopes in the A(H5N1) HA stem, vestigial esterase subdomain, and receptor binding site. This A(H5N1) H5-MNP IN and IM vaccine is immunogenic in female rodents and NHPs as a potential A(H5N1) pandemic single-dose vaccine.
External linksNat Commun / PubMed:40681543 / PubMed Central
MethodsEM (single particle)
Resolution3.23 - 3.38 Å
Structure data

EMDB-49222: Influenza A(H5N1) Clade 2.3.4.4b in complex with head specific monoclonal antibody NVX.361.4
Method: EM (single particle) / Resolution: 3.38 Å

EMDB-49235: Recombinant A(H5N1) A/American Wigeon/South Carolina/22/000345-001/2021 (A/AW/SC/2021) clade 2.3.4.4b nanoparticle in complex with mouse monoclonal antibody NVX.73.2
Method: EM (single particle) / Resolution: 3.23 Å

Source
  • H5N1 subtype (virus)
  • unidentified influenza virus
  • Mus musculus (house mouse)

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