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bioRxiv · 10.1101/2024.11.21.624712

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

Patel, N.·Rehman, A.·Frost, 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.·Smith, G.
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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 naive 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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Patel, N., Rehman, A., Frost, 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., Smith, G.. 2024-11-21. Single-dose avian influenza A(H5N1) Clade 2.3.4.4b hemagglutinin-Matrix-M nanoparticle vaccine induces neutralizing responses in nonhuman primates. https://doi.org/10.1101/2024.11.21.624712

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