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Cell Rep Med
. 2026 Jan 30:102582.
doi: 10.1016/j.xcrm.2025.102582. Online ahead of print.
An intranasal adenoviral-vectored vaccine protects against highly pathogenic avian influenza H5N1 in naive and antigen-experienced animals
Baoling Ying 1 , Kelly Pyles 1 , Tamarand L Darling 1 , Kuljeet Seehra 1 , Truc Pham 1 , Lin-Chen Huang 1 , Houda H Harastani 1 , Ashish Sharma 1 , Pritesh Desai 1 , Elena A Kashentseva 2 , David T Curiel 2 , Bjoern Peters 3 , James Brett Case 1 , Eva-Maria Strauch 4 , Michael S Diamond 5 , Adrianus C M Boon 6
Affiliations
The emergence of highly pathogenic avian H5N1 influenza viruses in dairy cows and humans has increased the potential for another pandemic. To address this risk, we developed chimpanzee adenoviral (ChAd)-vectored H5 hemagglutinin-targeted vaccines and tested their immunogenicity and efficacy in rodents. Immunization with ChAd-Texas (clade 2.3.4.4b) vaccine in mice elicits neutralizing antibody responses and confers protection against viral infection and mortality upon challenge with a human H5N1 isolate (A/Michigan/90/2024, clade 2.3.4.4b). Intranasal delivery of the ChAd-Texas vaccine elicits mucosal antibody and T cell responses and confers greater protection than intramuscular immunization. In Syrian hamsters, a single intranasal dose of ChAd-Texas vaccine prevents weight loss and reduces airway infection after H5N1 A/Michigan/90/2024 or A/Texas/37/2024 challenge. Importantly, prior seasonal influenza vaccination does not impair antibody responses or protection after intranasal delivery of the ChAd-Texas vaccine. These results support the development of mucosally administered ChAd-Texas HA vaccines as an effective platform for HPAI H5N1 preparedness.
Keywords: H5N1 influenza virus; Syrian hamster; chimpanzee-adenovirus vector; clade 2.3.4.4b; imprinting; mucosal vaccine; pre-existing immunity.
. 2026 Jan 30:102582.
doi: 10.1016/j.xcrm.2025.102582. Online ahead of print.
An intranasal adenoviral-vectored vaccine protects against highly pathogenic avian influenza H5N1 in naive and antigen-experienced animals
Baoling Ying 1 , Kelly Pyles 1 , Tamarand L Darling 1 , Kuljeet Seehra 1 , Truc Pham 1 , Lin-Chen Huang 1 , Houda H Harastani 1 , Ashish Sharma 1 , Pritesh Desai 1 , Elena A Kashentseva 2 , David T Curiel 2 , Bjoern Peters 3 , James Brett Case 1 , Eva-Maria Strauch 4 , Michael S Diamond 5 , Adrianus C M Boon 6
Affiliations
- PMID: 41619721
- DOI: 10.1016/j.xcrm.2025.102582
The emergence of highly pathogenic avian H5N1 influenza viruses in dairy cows and humans has increased the potential for another pandemic. To address this risk, we developed chimpanzee adenoviral (ChAd)-vectored H5 hemagglutinin-targeted vaccines and tested their immunogenicity and efficacy in rodents. Immunization with ChAd-Texas (clade 2.3.4.4b) vaccine in mice elicits neutralizing antibody responses and confers protection against viral infection and mortality upon challenge with a human H5N1 isolate (A/Michigan/90/2024, clade 2.3.4.4b). Intranasal delivery of the ChAd-Texas vaccine elicits mucosal antibody and T cell responses and confers greater protection than intramuscular immunization. In Syrian hamsters, a single intranasal dose of ChAd-Texas vaccine prevents weight loss and reduces airway infection after H5N1 A/Michigan/90/2024 or A/Texas/37/2024 challenge. Importantly, prior seasonal influenza vaccination does not impair antibody responses or protection after intranasal delivery of the ChAd-Texas vaccine. These results support the development of mucosally administered ChAd-Texas HA vaccines as an effective platform for HPAI H5N1 preparedness.
Keywords: H5N1 influenza virus; Syrian hamster; chimpanzee-adenovirus vector; clade 2.3.4.4b; imprinting; mucosal vaccine; pre-existing immunity.