Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Cell Rep. 2023 Apr 25;42(4):112326. doi: 10.1016/j.celrep.2023.112326. Epub 2023 Mar 30.
Group 2B β-coronaviruses (sarbecoviruses) have caused regional and global epidemics in modern history. Here, we evaluate the mechanisms of cross-sarbecovirus protective immunity, currently less clear yet important for pan-sarbecovirus vaccine development, using a panel of alphavirus-vectored vaccines covering bat to human strains. While vaccination does not prevent virus replication, it protects against lethal heterologous disease outcomes in both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clade 2 bat sarbecovirus challenge models. The spike vaccines tested primarily elicit a highly S1-specific homologous neutralizing antibody response with no detectable cross-virus neutralization. Rather, non-neutralizing antibody functions, mechanistically linked to FcgR4 and spike S2, mediate cross-protection in wild-type mice. Protection is lost in FcR knockout mice, further supporting a model for non-neutralizing, protective antibodies. These data highlight the importance of FcR-mediated cross-protective immune responses in universal pan-sarbecovirus vaccine designs.
β 属冠状病毒（沙贝科病毒）在现代历史上曾引发区域性和全球性流行。在这里，我们使用一组涵盖蝙蝠到人类株的甲病毒载体疫苗来评估交叉沙贝科病毒保护性免疫的机制，目前这种机制尚不清楚，但对于泛沙贝科病毒疫苗的开发很重要。虽然疫苗接种不能阻止病毒复制，但它可以预防严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）和 2 型蝙蝠沙贝科病毒属挑战模型中的致死性异种疾病结局。测试的刺突疫苗主要引发高度特异性 S1 的同源中和抗体反应，而没有检测到交叉病毒中和。相反，与 FcgR4 和刺突 S2 相关的非中和抗体功能介导了野生型小鼠中的交叉保护。在 FcR 敲除小鼠中失去了保护作用，进一步支持了非中和保护性抗体的模型。这些数据强调了 FcR 介导的交叉保护性免疫反应在通用泛沙贝科病毒疫苗设计中的重要性。
