tetano
Editor, Senior Moderator
NPJ Vaccines
. 2025 Jun 5;10(1):113.
doi: 10.1038/s41541-025-01178-x. Chimeric hemagglutinin and M2 mRNA vaccine for broad influenza subtype protection
Dongrong Yi[SUP] #[/SUP][SUP] 1 [/SUP], Qian Liu[SUP] #[/SUP][SUP] 1 [/SUP], Saisai Guo[SUP] #[/SUP][SUP] 1 [/SUP], Quanjie Li[SUP] #[/SUP][SUP] 1 [/SUP], Yongxin Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Ning Li[SUP] #[/SUP][SUP] 2 [/SUP], Qili Zhang[SUP] 2 [/SUP], Kai Lv[SUP] 1 [/SUP], Ni An[SUP] 3 [/SUP], Lu Han[SUP] 2 [/SUP], Hua Chen[SUP] 2 [/SUP], Yi Wang[SUP] 2 [/SUP], Chunyan Chang[SUP] 2 [/SUP], Huihan Shao[SUP] 1 [/SUP], Jing Wang[SUP] 1 [/SUP], Xiaoyu Li[SUP] 1 [/SUP], Linlin Bao[SUP] 4 [/SUP], Dayan Wang[SUP] 5 [/SUP], Guoyang Liao[SUP] 6 [/SUP], Chunjian Huang[SUP] 2 [/SUP], Weiguo Zhang[SUP] 7 [/SUP], Yijie Dong[SUP] 8 [/SUP], Yuelong Shu[SUP] 9 [/SUP], Shan Cen[SUP] 10 11 [/SUP]
Affiliations
Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics, developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy, we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs, as well as highly pathogenic avian influenza. Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies, T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries. In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells. Moreover, Fluaxe immunization inhibited the inflammatory response induced by influenza infection. In summary, we conclude that Fluaxe can elicit broad cross-protection against numerous influenza subtypes.
. 2025 Jun 5;10(1):113.
doi: 10.1038/s41541-025-01178-x. Chimeric hemagglutinin and M2 mRNA vaccine for broad influenza subtype protection
Dongrong Yi[SUP] #[/SUP][SUP] 1 [/SUP], Qian Liu[SUP] #[/SUP][SUP] 1 [/SUP], Saisai Guo[SUP] #[/SUP][SUP] 1 [/SUP], Quanjie Li[SUP] #[/SUP][SUP] 1 [/SUP], Yongxin Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Ning Li[SUP] #[/SUP][SUP] 2 [/SUP], Qili Zhang[SUP] 2 [/SUP], Kai Lv[SUP] 1 [/SUP], Ni An[SUP] 3 [/SUP], Lu Han[SUP] 2 [/SUP], Hua Chen[SUP] 2 [/SUP], Yi Wang[SUP] 2 [/SUP], Chunyan Chang[SUP] 2 [/SUP], Huihan Shao[SUP] 1 [/SUP], Jing Wang[SUP] 1 [/SUP], Xiaoyu Li[SUP] 1 [/SUP], Linlin Bao[SUP] 4 [/SUP], Dayan Wang[SUP] 5 [/SUP], Guoyang Liao[SUP] 6 [/SUP], Chunjian Huang[SUP] 2 [/SUP], Weiguo Zhang[SUP] 7 [/SUP], Yijie Dong[SUP] 8 [/SUP], Yuelong Shu[SUP] 9 [/SUP], Shan Cen[SUP] 10 11 [/SUP]
Affiliations
- PMID: 40473642
- PMCID: PMC12141470
- DOI: 10.1038/s41541-025-01178-x
Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics, developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy, we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs, as well as highly pathogenic avian influenza. Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies, T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries. In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells. Moreover, Fluaxe immunization inhibited the inflammatory response induced by influenza infection. In summary, we conclude that Fluaxe can elicit broad cross-protection against numerous influenza subtypes.