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Commun Biol
. 2026 Jan 7.
doi: 10.1038/s42003-025-09451-4. Online ahead of print. Enhancing the breadth of protection in mice with a multivalent influenza vaccine
Xiang Wang 1 , Yixin Niu 1 , Ying Hu 1 , Caihong Zhu 1 , Xi Yang 1 , Hongyang Shi 2 , Yao Yan 1 , Ping Zhou 2 , Longfei Ding 1 , Miaomiao Zhang 1 , Mangteng Wu 3 , Shubing Tang 4 , Man Xing 5 , Dongming Zhou 6 7
Affiliations
The high mutation rate of the influenza virus poses a significant challenge to global health, highlighting the urgent need for broad-spectrum vaccines. Here, we engineered Ad-Hex, a pan-influenza vaccine comprising three chimpanzee adenoviral vectors (Ad-H1H3, Ad-BYBV, and Ad-H5H7), each encoding the hemagglutinin (HA) genes from two distinct influenza virus subtypes/lineages in the △E1 region. A single intranasal dose of Ad-Hex induced robust humoral, cellular, and mucosal immunity, conferring complete protection against lethal challenge with six vaccine-matched strains in female C57BL/6 or Balb/c mice. Notably, the vaccine achieved 60% survival rates against mismatched strains. Mechanistic studies revealed that Ad-Hex activated germinal center B-cell responses not only against the cognate HAs but also against the conserved HA stalks. This drove the production of cross-reactive antibodies, which contributed to heterologous protection along with the CD8+ T cell response. Our study confirms the feasibility of this multivalent strategy by mixing multiple recombinant adenoviruses and provides insights into the development of multivalent vaccines against other respiratory pathogens.
. 2026 Jan 7.
doi: 10.1038/s42003-025-09451-4. Online ahead of print. Enhancing the breadth of protection in mice with a multivalent influenza vaccine
Xiang Wang 1 , Yixin Niu 1 , Ying Hu 1 , Caihong Zhu 1 , Xi Yang 1 , Hongyang Shi 2 , Yao Yan 1 , Ping Zhou 2 , Longfei Ding 1 , Miaomiao Zhang 1 , Mangteng Wu 3 , Shubing Tang 4 , Man Xing 5 , Dongming Zhou 6 7
Affiliations
- PMID: 41501378
- DOI: 10.1038/s42003-025-09451-4
The high mutation rate of the influenza virus poses a significant challenge to global health, highlighting the urgent need for broad-spectrum vaccines. Here, we engineered Ad-Hex, a pan-influenza vaccine comprising three chimpanzee adenoviral vectors (Ad-H1H3, Ad-BYBV, and Ad-H5H7), each encoding the hemagglutinin (HA) genes from two distinct influenza virus subtypes/lineages in the △E1 region. A single intranasal dose of Ad-Hex induced robust humoral, cellular, and mucosal immunity, conferring complete protection against lethal challenge with six vaccine-matched strains in female C57BL/6 or Balb/c mice. Notably, the vaccine achieved 60% survival rates against mismatched strains. Mechanistic studies revealed that Ad-Hex activated germinal center B-cell responses not only against the cognate HAs but also against the conserved HA stalks. This drove the production of cross-reactive antibodies, which contributed to heterologous protection along with the CD8+ T cell response. Our study confirms the feasibility of this multivalent strategy by mixing multiple recombinant adenoviruses and provides insights into the development of multivalent vaccines against other respiratory pathogens.