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Single-dose avian influenza A(H5N1) Clade 2.3.4.4b hemagglutinin–Matrix-M® nanoparticle vaccine induces neutralizing responses in nonhuman primates

Author

Listed:
  • Nita Patel

    (Inc.)

  • Asma Rehman

    (Inc.)

  • Jessica F. Trost

    (Inc.)

  • Rhonda Flores

    (Inc.)

  • Zach Longacre

    (Inc.)

  • Mimi Guebre-Xabier

    (Inc.)

  • Haixia Zhou

    (Inc.)

  • Bin Zhou

    (Inc.)

  • Kelsey Jacobson

    (Inc.)

  • Desheng Jiang

    (Inc.)

  • Xiaoyun Bai

    (Inc.)

  • Rafia Khatoon

    (Inc.)

  • Thomas Kort

    (Inc.)

  • James Norton

    (Inc.)

  • M. Madhangi

    (Inc.)

  • Melinda Hersey

    (Inc.)

  • Ann M. Greene

    (Inc.)

  • Filip Dubovsky

    (Inc.)

  • Gale Smith

    (Inc.)

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 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.

Suggested Citation

  • Nita 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 , 2025. "Single-dose avian influenza A(H5N1) Clade 2.3.4.4b hemagglutinin–Matrix-M® nanoparticle vaccine induces neutralizing responses in nonhuman primates," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61964-y
    DOI: 10.1038/s41467-025-61964-y
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    References listed on IDEAS

    as
    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
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    3. Jing-Hui Tian & Nita Patel & Robert Haupt & Haixia Zhou & Stuart Weston & Holly Hammond & James Logue & Alyse D. Portnoff & James Norton & Mimi Guebre-Xabier & Bin Zhou & Kelsey Jacobson & Sonia Macie, 2021. "SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
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