Single-dose avian influenza A(H5N1) Clade 2.3.4.4b hemagglutinin–Matrix-M® nanoparticle vaccine induces neutralizing responses in nonhuman primates
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...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61964-y |
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| author | 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 James Norton M. Madhangi Melinda Hersey Ann M. Greene Filip Dubovsky Gale Smith |
| author_facet | 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 James Norton M. Madhangi Melinda Hersey Ann M. Greene Filip Dubovsky Gale Smith |
| author_sort | Nita Patel |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0e2fea8564ab46dcb5be013a12c7335e |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-0e2fea8564ab46dcb5be013a12c7335e2025-08-20T03:05:06ZengNature PortfolioNature Communications2041-17232025-07-0116111610.1038/s41467-025-61964-ySingle-dose avian influenza A(H5N1) Clade 2.3.4.4b hemagglutinin–Matrix-M® nanoparticle vaccine induces neutralizing responses in nonhuman primatesNita Patel0Asma Rehman1Jessica F. Trost2Rhonda Flores3Zach Longacre4Mimi Guebre-Xabier5Haixia Zhou6Bin Zhou7Kelsey Jacobson8Desheng Jiang9Xiaoyun Bai10Rafia Khatoon11Thomas Kort12James Norton13M. Madhangi14Melinda Hersey15Ann M. Greene16Filip Dubovsky17Gale Smith18Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, Inc.Novavax, 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.https://doi.org/10.1038/s41467-025-61964-y |
| spellingShingle | 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 James Norton M. Madhangi Melinda Hersey Ann M. Greene Filip Dubovsky Gale Smith Single-dose avian influenza A(H5N1) Clade 2.3.4.4b hemagglutinin–Matrix-M® nanoparticle vaccine induces neutralizing responses in nonhuman primates Nature Communications |
| title | Single-dose avian influenza A(H5N1) Clade 2.3.4.4b hemagglutinin–Matrix-M® nanoparticle vaccine induces neutralizing responses in nonhuman primates |
| title_full | Single-dose avian influenza A(H5N1) Clade 2.3.4.4b hemagglutinin–Matrix-M® nanoparticle vaccine induces neutralizing responses in nonhuman primates |
| title_fullStr | Single-dose avian influenza A(H5N1) Clade 2.3.4.4b hemagglutinin–Matrix-M® nanoparticle vaccine induces neutralizing responses in nonhuman primates |
| title_full_unstemmed | Single-dose avian influenza A(H5N1) Clade 2.3.4.4b hemagglutinin–Matrix-M® nanoparticle vaccine induces neutralizing responses in nonhuman primates |
| title_short | Single-dose avian influenza A(H5N1) Clade 2.3.4.4b hemagglutinin–Matrix-M® nanoparticle vaccine induces neutralizing responses in nonhuman primates |
| title_sort | single dose avian influenza a h5n1 clade 2 3 4 4b hemagglutinin matrix m r nanoparticle vaccine induces neutralizing responses in nonhuman primates |
| url | https://doi.org/10.1038/s41467-025-61964-y |
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