tetano
Editor, Senior Moderator
EBioMedicine
. 2026 Aug 11:131:106430.
doi: 10.1016/j.ebiom.2026.106430. Online ahead of print.
Protective effect of A(H5N8) stockpiled vaccine against a virus genetically identical to a human isolate of bovine A(H5N1) influenza virus
Ryuta Uraki[SUP] 1 [/SUP], Maki Kiso[SUP] 2 [/SUP], Kiyoko Iwatsuki-Horimoto[SUP] 3 [/SUP], Mutsumi Ito[SUP] 4 [/SUP], Seiya Yamayoshi[SUP] 5 [/SUP], Masaki Imai[SUP] 6 [/SUP], Yoshihiro Kawaoka[SUP] 7 [/SUP]
Affiliations
Background: Since early 2024, highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b have caused extensive outbreaks in dairy cattle in the United States, with spillover into mammalian species, including humans. A bovine-derived A(H5N1) virus isolated from a human case retains high pathogenicity and transmissibility in mammalian models, highlighting its pandemic potential. Stockpiled pre-pandemic influenza vaccines are intended to provide early protection before strain-matched vaccines are available; however, their protective efficacy against bovine A(H5N1) viruses has not been directly evaluated in vivo.
Methods: In this study, we assessed the protective efficacy of an AS03-adjuvanted A/Astrakhan/3212/2020 (H5N8) clade 2.3.4.4b-based influenza vaccine stockpiled in Japan using mouse and ferret models. Vaccinated and unvaccinated animals were challenged with a virus genetically identical to a human isolate of bovine A(H5N1) virus. Neutralising antibody responses, viral replication in organs, and survival were evaluated.
Findings: Vaccination with the AS03-adjuvanted A(H5N8)-based stockpiled vaccine induced robust neutralising antibody responses in both animal models, significantly suppressed viral replication, and conferred complete protection against lethal challenge. In contrast, all unvaccinated mice and ferrets succumbed to infection. These findings demonstrate that the AS03-adjuvanted A(H5N8)-based stockpiled vaccine provides strong cross-protective efficacy against bovine A(H5N1) viruses.
Interpretation: An AS03-adjuvanted A(H5N8)-based vaccine stockpiled in Japan could serve as an immediate countermeasure against bovine A(H5N1) viruses during the early phase of a pandemic.
Funding: This work was supported by grants from the Japan Program for Infectious Diseases Research and Infrastructure (JP20wm0125002) and the Japan Initiative for World-leading Vaccine Research and Development Centers (JP223fa627001) from the Japan Agency for Medical Research and Development.
Keywords: Bovine A(H5N1) influenza virus; Ferret model; Mouse model; Stockpiled vaccine.
. 2026 Aug 11:131:106430.
doi: 10.1016/j.ebiom.2026.106430. Online ahead of print.
Protective effect of A(H5N8) stockpiled vaccine against a virus genetically identical to a human isolate of bovine A(H5N1) influenza virus
Ryuta Uraki[SUP] 1 [/SUP], Maki Kiso[SUP] 2 [/SUP], Kiyoko Iwatsuki-Horimoto[SUP] 3 [/SUP], Mutsumi Ito[SUP] 4 [/SUP], Seiya Yamayoshi[SUP] 5 [/SUP], Masaki Imai[SUP] 6 [/SUP], Yoshihiro Kawaoka[SUP] 7 [/SUP]
Affiliations
- PMID: 42580038
- DOI: 10.1016/j.ebiom.2026.106430
Background: Since early 2024, highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b have caused extensive outbreaks in dairy cattle in the United States, with spillover into mammalian species, including humans. A bovine-derived A(H5N1) virus isolated from a human case retains high pathogenicity and transmissibility in mammalian models, highlighting its pandemic potential. Stockpiled pre-pandemic influenza vaccines are intended to provide early protection before strain-matched vaccines are available; however, their protective efficacy against bovine A(H5N1) viruses has not been directly evaluated in vivo.
Methods: In this study, we assessed the protective efficacy of an AS03-adjuvanted A/Astrakhan/3212/2020 (H5N8) clade 2.3.4.4b-based influenza vaccine stockpiled in Japan using mouse and ferret models. Vaccinated and unvaccinated animals were challenged with a virus genetically identical to a human isolate of bovine A(H5N1) virus. Neutralising antibody responses, viral replication in organs, and survival were evaluated.
Findings: Vaccination with the AS03-adjuvanted A(H5N8)-based stockpiled vaccine induced robust neutralising antibody responses in both animal models, significantly suppressed viral replication, and conferred complete protection against lethal challenge. In contrast, all unvaccinated mice and ferrets succumbed to infection. These findings demonstrate that the AS03-adjuvanted A(H5N8)-based stockpiled vaccine provides strong cross-protective efficacy against bovine A(H5N1) viruses.
Interpretation: An AS03-adjuvanted A(H5N8)-based vaccine stockpiled in Japan could serve as an immediate countermeasure against bovine A(H5N1) viruses during the early phase of a pandemic.
Funding: This work was supported by grants from the Japan Program for Infectious Diseases Research and Infrastructure (JP20wm0125002) and the Japan Initiative for World-leading Vaccine Research and Development Centers (JP223fa627001) from the Japan Agency for Medical Research and Development.
Keywords: Bovine A(H5N1) influenza virus; Ferret model; Mouse model; Stockpiled vaccine.