Hajnik Renee L, Plante Jessica A, Reddy Bonam Srinivasa, Rafael Grace H, Liang Yuejin, Hazell Nicholas C, Walker Jordyn, Reyna Rachel A, Walker David H, Alameh Mohamad-Gabriel, Weissman Drew, Weaver Scott C, Plante Kenneth S, Hu Haitao
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
NPJ Vaccines. 2024 Sep 4;9(1):160. doi: 10.1038/s41541-024-00957-2.
While first-generation, spike (S)-based COVID-19 vaccines were effective against early SARS-CoV-2 strains, the rapid evolution of novel Omicron subvariants have substantially reduced vaccine efficacy. As such, broadly protective vaccines against SARS-CoV-2 are needed to prevent future viral emergence. In addition, it remains less clear whether peripheral immunization, especially with mRNA vaccines, elicits effective respiratory immunity. Our group has developed a nucleoside-modified mRNA vaccine expressing the nucleocapsid (N) protein of the ancestral SARS-CoV-2 virus and has tested its use in combination with the S-based mRNA vaccine (mRNA-S). In this study, we examined efficacy of mRNA-N alone or in combination with mRNA-S (mRNA-S+N) against more immune evasive Omicron variants in hamsters. Our data show that mRNA-N alone induces a modest but significant protection against BA.5 and that dual mRNA-S+N vaccination confers complete protection against both BA.5 and BQ.1, preventing detection of virus in the hamster lungs. Analysis of respiratory immune response in mice shows that intramuscular mRNA-S+N immunization effectively induces respiratory S- and N-specific T cell responses in the lungs and in bronchoalveolar lavage (BAL), as well as antigen-specific binding IgG in BAL. Together, our data further support mRNA-S+N as a potential pan-COVID-19 vaccine for broad protection against current and emerging SARS-CoV-2 variants.
虽然第一代基于刺突（S）蛋白的新冠疫苗对早期的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）毒株有效，但新型奥密克戎亚变体的快速进化已大幅降低了疫苗效力。因此，需要能够提供广泛保护的SARS-CoV-2疫苗来预防未来病毒的出现。此外，外周免疫，尤其是mRNA疫苗免疫，是否能引发有效的呼吸道免疫仍不太明确。我们团队研发了一种表达原始SARS-CoV-2病毒核衣壳（N）蛋白的核苷修饰mRNA疫苗，并测试了其与基于S蛋白的mRNA疫苗（mRNA-S）联合使用的效果。在本研究中，我们检测了单独使用mRNA-N或与mRNA-S联合使用（mRNA-S+N）对仓鼠体内更具免疫逃逸能力的奥密克戎变体的效力。我们的数据表明，单独使用mRNA-N可对BA.5毒株产生适度但显著的保护作用，而mRNA-S+N联合疫苗接种则可对BA.5和BQ.1毒株提供完全保护，防止在仓鼠肺部检测到病毒。对小鼠呼吸道免疫反应的分析表明，肌肉注射mRNA-S+N可有效诱导肺部和支气管肺泡灌洗（BAL）液中针对S和N蛋白的特异性T细胞反应，以及BAL液中的抗原特异性结合IgG。总之，我们的数据进一步支持mRNA-S+N作为一种潜在的全新冠疫苗，可广泛预防当前及新出现的SARS-CoV-2变体。
