tetano
Editor, Senior Moderator
Cell Rep Med
. 2026 Apr 2:102702.
doi: 10.1016/j.xcrm.2026.102702. Online ahead of print.
Preclinical evaluation of an mRNA vaccine developed from the first human isolate of bovine H5N1
Hongli Li[SUP] 1 [/SUP], Mengting Huang[SUP] 1 [/SUP], Simin Feng[SUP] 2 [/SUP], Wansheng Li[SUP] 1 [/SUP], Dandan Wei[SUP] 3 [/SUP], Xuechun Li[SUP] 4 [/SUP], Yun Quan[SUP] 1 [/SUP], Hao Gu[SUP] 5 [/SUP], Ting Jiang[SUP] 5 [/SUP], Yan Liu[SUP] 5 [/SUP], Jing Lu[SUP] 5 [/SUP], Wenjun Song[SUP] 6 [/SUP], Xinkui Zhang[SUP] 3 [/SUP], Yujia Yang[SUP] 3 [/SUP], Qianyu Pan[SUP] 1 [/SUP], LinLei Chen[SUP] 7 [/SUP], Jingyou Yu[SUP] 1 [/SUP], Hantao Lou[SUP] 8 [/SUP], Mengyi Zhang[SUP] 9 [/SUP], Youchun Wang[SUP] 9 [/SUP], Kelvin Kai-Wang To[SUP] 7 [/SUP], Weixin Jia[SUP] 10 [/SUP], Jinzhong Lin[SUP] 11 [/SUP], Qiong Zhang[SUP] 12 [/SUP]
Affiliations
Given the global threat posed by H5N1 clade 2.3.4.4b avian influenza, rapid development of effective vaccines is imperative. We design an mRNA vaccine encoding hemagglutinin (HA) from A/Texas/37/2024, the first bovine-to-human strain. In murine models, both wild-type and cleavage-site-modified HA vaccines elicit robust and durable humoral immunity, along with a balanced Th1/Th2 response, conferring complete protection against lethal homologous viral challenge. The vaccine, along with the World Health Organization (WHO)-recommended candidate (A/Astrakhan/3212/2020), elicits cross-clade binding antibody responses and demonstrates improvement against specific clades at a 1 μg dose. Pre-existing H1 immunity does not diminish H5-specific immunogenicity. In avian species, the vaccine also provides full protection against lethal clades (2.3.4.4b and 2.3.4.4h). Formulated with another ionizable lipid, the vaccine elicits responses comparable to benchmark lipid nanoparticles (LNPs) and shows a favorable safety profile in rats. This work establishes a rapidly adaptable mRNA-LNP vaccine prototype for pandemic preparedness against evolving avian influenza threats.
Keywords: H5N1 mRNA vaccine; bovine H5N1; clade 2.3.4.4b; cross-clade protection; ionizable lipid.
. 2026 Apr 2:102702.
doi: 10.1016/j.xcrm.2026.102702. Online ahead of print.
Preclinical evaluation of an mRNA vaccine developed from the first human isolate of bovine H5N1
Hongli Li[SUP] 1 [/SUP], Mengting Huang[SUP] 1 [/SUP], Simin Feng[SUP] 2 [/SUP], Wansheng Li[SUP] 1 [/SUP], Dandan Wei[SUP] 3 [/SUP], Xuechun Li[SUP] 4 [/SUP], Yun Quan[SUP] 1 [/SUP], Hao Gu[SUP] 5 [/SUP], Ting Jiang[SUP] 5 [/SUP], Yan Liu[SUP] 5 [/SUP], Jing Lu[SUP] 5 [/SUP], Wenjun Song[SUP] 6 [/SUP], Xinkui Zhang[SUP] 3 [/SUP], Yujia Yang[SUP] 3 [/SUP], Qianyu Pan[SUP] 1 [/SUP], LinLei Chen[SUP] 7 [/SUP], Jingyou Yu[SUP] 1 [/SUP], Hantao Lou[SUP] 8 [/SUP], Mengyi Zhang[SUP] 9 [/SUP], Youchun Wang[SUP] 9 [/SUP], Kelvin Kai-Wang To[SUP] 7 [/SUP], Weixin Jia[SUP] 10 [/SUP], Jinzhong Lin[SUP] 11 [/SUP], Qiong Zhang[SUP] 12 [/SUP]
Affiliations
- PMID: 41950927
- DOI: 10.1016/j.xcrm.2026.102702
Given the global threat posed by H5N1 clade 2.3.4.4b avian influenza, rapid development of effective vaccines is imperative. We design an mRNA vaccine encoding hemagglutinin (HA) from A/Texas/37/2024, the first bovine-to-human strain. In murine models, both wild-type and cleavage-site-modified HA vaccines elicit robust and durable humoral immunity, along with a balanced Th1/Th2 response, conferring complete protection against lethal homologous viral challenge. The vaccine, along with the World Health Organization (WHO)-recommended candidate (A/Astrakhan/3212/2020), elicits cross-clade binding antibody responses and demonstrates improvement against specific clades at a 1 μg dose. Pre-existing H1 immunity does not diminish H5-specific immunogenicity. In avian species, the vaccine also provides full protection against lethal clades (2.3.4.4b and 2.3.4.4h). Formulated with another ionizable lipid, the vaccine elicits responses comparable to benchmark lipid nanoparticles (LNPs) and shows a favorable safety profile in rats. This work establishes a rapidly adaptable mRNA-LNP vaccine prototype for pandemic preparedness against evolving avian influenza threats.
Keywords: H5N1 mRNA vaccine; bovine H5N1; clade 2.3.4.4b; cross-clade protection; ionizable lipid.