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Peer-reviewedCC BY-NC-ND 4.0NPJ Vaccines

Intranasal and intramuscular H5-Matrix-M nanoparticle vaccines protects against highly pathogenic H5N1 influenza virus in mice

  • Kelly Pyles1
  • Tamarand L. Darling1
  • Lin-Chen Huang1
  • Mimi Guebre-Xabier2
  • Melinda Hersey2
  • Ann M. Greene2
  • Nita Patel2
  • Gale Smith2
  • Adrianus C. M. Boon1,3,4,5
5 affiliations
  1. 1Department of Medicine, Washington University School of Medicine, St. Louis, MO USA
  2. 2Novavax, Inc., Gaithersburg, MD USA
  3. 3Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO USA
  4. 4Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO USA
  5. 5Andrew M. and Jane M. Bursky the Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO USA
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Abstract

The emergence of clade 2.3.4.4b highly pathogenic H5N1 influenza virus in dairy cows and transmission to humans has heightened public health concerns. In this work, we characterized the immunogenicity and efficacy of a Matrix-M®–adjuvanted nanoparticle protein vaccine containing recombinant H5 HA of A/American wigeon/South Carolina/22/000345-001/2021 virus (clade 2.3.4.4b, H5-MNP). In naïve mice, intranasal or intramuscular vaccination with H5-MNP induced robust H5 binding and virus neutralizing antibody responses and protected against a lethal H5N1 challenge (A/Michigan/90/2024, clade 2.3.4.4b). In mice primed with seasonal influenza vaccine, one dose of H5-MNP vaccine provided similar levels of protection, with fewer breakthrough infections detected in the upper airways of mice that received the H5-MNP intranasally compared to those that were immunized intramuscularly. This novel H5-MNP vaccine technology could potentially induce protective immunity against pandemic influenza viruses in individuals with pre-existing seasonal influenza HA immunity.

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Cite

BibTeXRIS
BibTeX
@article{pyles2026intranasal,
  title = {{Intranasal and intramuscular H5-Matrix-M nanoparticle vaccines protects against highly pathogenic H5N1 influenza virus in mice}},
  author = {Kelly Pyles and Tamarand L. Darling and Lin-Chen Huang and Mimi Guebre-Xabier and Melinda Hersey and Ann M. Greene and Nita Patel and Gale Smith and Adrianus C. M. Boon},
  journal = {NPJ Vaccines},
  year = {2026},
  month = jul,
  doi = {10.1038/s41541-026-01523-8},
  url = {https://doi.org/10.1038/s41541-026-01523-8},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Intranasal and intramuscular H5-Matrix-M nanoparticle vaccines protects against highly pathogenic H5N1 influenza virus in mice
AU  - Kelly Pyles
AU  - Tamarand L. Darling
AU  - Lin-Chen Huang
AU  - Mimi Guebre-Xabier
AU  - Melinda Hersey
AU  - Ann M. Greene
AU  - Nita Patel
AU  - Gale Smith
AU  - Adrianus C. M. Boon
PY  - 2026
DA  - 2026/07/10
JO  - NPJ Vaccines
DO  - 10.1038/s41541-026-01523-8
UR  - https://doi.org/10.1038/s41541-026-01523-8
AB  - The emergence of clade 2.3.4.4b highly pathogenic H5N1 influenza virus in dairy cows and transmission to humans has heightened public health concerns. In this work, we characterized the immunogenicity and efficacy of a Matrix-M®–adjuvanted nanoparticle protein vaccine containing recombinant H5 HA of A/American wigeon/South Carolina/22/000345-001/2021 virus (clade 2.3.4.4b, H5-MNP). In naïve mice, intranasal or intramuscular vaccination with H5-MNP induced robust H5 binding and virus neutralizing antibody responses and protected against a lethal H5N1 challenge (A/Michigan/90/2024, clade 2.3.4.4b). In mice primed with seasonal influenza vaccine, one dose of H5-MNP vaccine provided similar levels of protection, with fewer breakthrough infections detected in the upper airways of mice that received the H5-MNP intranasally compared to those that were immunized intramuscularly. This novel H5-MNP vaccine technology could potentially induce protective immunity against pandemic influenza viruses in individuals with pre-existing seasonal influenza HA immunity.
SN  - 2059-0105
ER  -