A chimeric mRNA vaccine of S-RBD with HA conferring broad protection against influenza and COVID-19 variants

作者：Tianjiao Hao, Yulei Li, Peipei Liu, X. L. Wang, Ke Xu, Wenwen Lei, Ying Li, Rong Zhang, Xiaoyan Li, Xin Zhao, Kun Xu, Xuancheng Lu, Yuhai Bi, Hao Song, Guizhen Wu, Baoli Zhu, George F. Gao · 发表于：PLoS Pathogens · 年份：2024 · DOI：10.1371/journal.ppat.1012508 · 被引用次数：6 · 研究领域：Influenza Virus Research Studies、Respiratory viral infections research、SARS-CoV-2 and COVID-19 Research

Influenza and coronavirus disease 2019 (COVID-19) represent two respiratory diseases that have significantly impacted global health, resulting in substantial disease burden and mortality. An optimal solution would be a combined vaccine capable of addressing both diseases, thereby obviating the need for multiple vaccinations. Previously, we conceived a chimeric protein subunit vaccine targeting both influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), utilizing the receptor binding domain of spike protein (S-RBD) and the stalk region of hemagglutinin protein (HA-stalk) components. By integrating the S-RBD from the SARS-CoV-2 Delta variant with the headless hemagglutinin (HA) from H1N1 influenza virus, we constructed stable trimeric structures that remain accessible to neutralizing antibodies. This vaccine has demonstrated its potential by conferring protection against a spectrum of strains in mouse models. In this study, we designed an mRNA vaccine candidate encoding the chimeric antigen. The resultant humoral and cellular immune responses were meticulously evaluated in mouse models. Furthermore, the protective efficacy of the vaccine was rigorously examined through challenges with either homologous or heterologous influenza viruses or SARS-CoV-2 strains. Our findings reveal that the mRNA vaccine exhibited robust immunogenicity, engendering high and sustained levels of neutralizing antibodies accompanied by robust and persistent cellular immunity. ...