PDF(Pubmed)
Abstract：
Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response.
摘要：
异源初免-加强打破了COVID-19疫苗的保护性免疫应答瓶颈。然而,潜在的机制尚未完全阐明。这里,我们研究了抗体反应,并探讨了生发中心(GC)对小鼠用灭活疫苗引发和用异源腺病毒载体疫苗或同源灭活疫苗增强的反应.两种增强方案都显著增强了抗体应答。异源免疫诱导更强大的GC激活，以Tfh细胞群增加和辅助功能增强为特征。此外,在异源方案中观察到B细胞活化和抗体产生增加.Libra-seq用于比较S1-，同源和异源疫苗接种之间的S2和NTD特异性B细胞，分别。S2特异性CD19+B细胞呈现增加的体细胞超突变（SHM），主要富集在浆细胞中。此外，异源加强剂量促进了对S2和NTD区域特异性的B细胞的克隆扩增。总之,SARS-CoV-2异源疫苗接种后Tfh和B细胞的功能作用可能对调节抗体应答很重要。这些发现为开发诱导更强大的抗体反应的SARS-CoV-2疫苗提供了新的见解。
