严重急性呼吸综合征(SARS)-冠状病毒(CoV),中东呼吸综合征(MERS)-CoV,SARS-CoV-2已经严重威胁了21世纪的人类生命。2019年冠状病毒病(COVID-19)流行后,新兴和重新出现的β-冠状病毒仍然是可能危害人类健康的高致病性病原体。因此,迫切需要泛β-冠状病毒疫苗策略来应对即将到来的危险。在这项研究中,四种LNP-mRNA疫苗,名为O,D,S,M,针对SARS-CoV-2Omicron的刺突蛋白,Delta,SARS-CoV,还有MERS-CoV,分别,合成并表征纯度和完整性。所有四种LNP-mRNA在小鼠中诱导针对相应刺突蛋白抗原的有效细胞和体液免疫应答。此外,LNP-mRNAS和D诱导了针对SARS-CoV和SARS-CoV-2的中和抗体,这些抗体未能与MERS-CoV发生交叉反应。随后用LNP-mRNAO进行顺序和鸡尾酒免疫的评估,D,S,M有效地引发了针对SARS-CoV-2变体的广泛免疫,SARS-CoV,还有MERS-CoV.顺序与鸡尾酒方案的直接比较表明,鸡尾酒疫苗接种策略诱导了针对异型病毒的更有效的中和抗体和T细胞反应,以及针对泛β冠状病毒的更广泛的抗体活性。总的来说,这些结果提供了一种潜在的泛β-冠状病毒疫苗策略,以改善未来冠状病毒威胁之前的准备.
Severe acute respiratory syndrome (SARS)-coronavirus (CoV), Middle Eastern respiratory syndrome (MERS)-CoV, and SARS-CoV-2 have seriously threatened human life in the 21st century. Emerging and re-emerging β-coronaviruses after the coronavirus disease 2019 (COVID-19) epidemic remain possible highly pathogenic agents that can endanger human health. Thus, pan-β-coronavirus vaccine strategies to combat the upcoming dangers are urgently needed. In this study, four LNP-mRNA vaccines, named O, D, S, and M, targeting the spike protein of SARS-CoV-2 Omicron, Delta, SARS-CoV, and MERS-CoV, respectively, were synthesized and characterized for purity and integrity. All four LNP-mRNAs induced effective cellular and humoral immune responses against the corresponding spike protein antigens in mice. Furthermore, LNP-mRNA S and D induced neutralizing antibodies against SARS-CoV and SARS-CoV-2, which failed to cross-react with MERS-CoV. Subsequent evaluation of sequential and cocktail immunizations with LNP-mRNA O, D, S, and M effectively elicited broad immunity against SARS-CoV-2 variants, SARS-CoV, and MERS-CoV. A direct comparison of the sequential with cocktail regimens indicated that the cocktail vaccination strategy induced more potent neutralizing antibodies and T-cell responses against heterotypic viruses as well as broader antibody activity against pan-β-coronaviruses. Overall, these results present a potential pan-β-coronavirus vaccine strategy for improved preparedness prior to future coronavirus threats.