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Peer-reviewedCC BY 4.0Frontiers in Immunology

An adenovirus-based mucosal vaccine induces cross-neutralizing antibodies and protects against lethal H5N1 infection in ferrets

  • Becca A. Flitter1
  • Kayan Tam1
  • Laura J. Showalter1
  • William Sun1
  • Sean N. Tucker1
  1. 1Vaxart, Inc.
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Abstract

Background: H5N1 highly pathogenic avian influenza (HPAI) has been detected in multiple animal species, including humans, posing a significant threat to public health. Vaccines capable of eliciting robust mucosal and systemic immunity are needed to protect against HPAI infection.

Methods: First- and second-generation non-replicating adenovirus type-5 vectored vaccines expressing hemagglutinin (HA) from clade 2.1.3.2 (ND1.1) and clade 2.3.4.4b (VXA-H5-02), were administered via peroral route to ferrets. Mucosal and systemic immunogenicity were evaluated. Protective efficacy, viral burden, and shedding was assessed against clade 2.3.4.4b challenge, for clade-matched VXA-H5–02 and clade-mismatched ND1.1 vaccines.

Results: Immunization elicited mucosal immunity and serum neutralizing activity in ferrets against homologous and heterologous clades. All control animals rapidly succumbed to the lethal 2.3.4.4b clade challenge, compared with survival rates of 38% and 100% in the ND1.1 and VXA-H5–02 vaccine groups, respectively. VXA-H5–02 immunization significantly reduced illness, viral burden, and shedding.

Conclusion: Second-generation VXA-H5–02 is a promising vaccine candidate capable of inducing systemic and mucosal immunity, offering broad protection against HPAI.

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Cite

BibTeXRIS
BibTeX
@article{flitter2026adenovirusbased,
  title = {{An adenovirus-based mucosal vaccine induces cross-neutralizing antibodies and protects against lethal H5N1 infection in ferrets}},
  author = {Becca A. Flitter and Kayan Tam and Laura J. Showalter and William Sun and Sean N. Tucker},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1863888},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1863888/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - An adenovirus-based mucosal vaccine induces cross-neutralizing antibodies and protects against lethal H5N1 infection in ferrets
AU  - Becca A. Flitter
AU  - Kayan Tam
AU  - Laura J. Showalter
AU  - William Sun
AU  - Sean N. Tucker
PY  - 2026
DA  - 2026/10/08
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1863888
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1863888/full
AB  - Background: H5N1 highly pathogenic avian influenza (HPAI) has been detected in multiple animal species, including humans, posing a significant threat to public health. Vaccines capable of eliciting robust mucosal and systemic immunity are needed to protect against HPAI infection.  Methods: First- and second-generation non-replicating adenovirus type-5 vectored vaccines expressing hemagglutinin (HA) from clade 2.1.3.2 (ND1.1) and clade 2.3.4.4b (VXA-H5-02), were administered via peroral route to ferrets. Mucosal and systemic immunogenicity were evaluated. Protective efficacy, viral burden, and shedding was assessed against clade 2.3.4.4b challenge, for clade-matched VXA-H5–02 and clade-mismatched ND1.1 vaccines.  Results: Immunization elicited mucosal immunity and serum neutralizing activity in ferrets against homologous and heterologous clades. All control animals rapidly succumbed to the lethal 2.3.4.4b clade challenge, compared with survival rates of 38% and 100% in the ND1.1 and VXA-H5–02 vaccine groups, respectively. VXA-H5–02 immunization significantly reduced illness, viral burden, and shedding.  Conclusion: Second-generation VXA-H5–02 is a promising vaccine candidate capable of inducing systemic and mucosal immunity, offering broad protection against HPAI.
SN  - 1664-3224
ER  -