Marzi Roberta, Bassi Jessica, Silacci-Fregni Chiara, Bartha Istvan, Muoio Francesco, Culap Katja, Sprugasci Nicole, Lombardo Gloria, Saliba Christian, Cameroni Elisabetta, Cassotta Antonino, Low Jun Siong, Walls Alexandra C, McCallum Matthew, Tortorici M Alejandra, Bowen John E, Dellota Exequiel A, Dillen Josh R, Czudnochowski Nadine, Pertusini Laura, Terrot Tatiana, Lepori Valentino, Tarkowski Maciej, Riva Agostino, Biggiogero Maira, Franzetti-Pellanda Alessandra, Garzoni Christian, Ferrari Paolo, Ceschi Alessandro, Giannini Olivier, Havenar-Daughton Colin, Telenti Amalio, Arvin Ann, Virgin Herbert W, Sallusto Federica, Veesler David, Lanzavecchia Antonio, Corti Davide, Piccoli Luca
Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
iScience. 2023 Jan 20;26(1):105726. doi: 10.1016/j.isci.2022.105726. Epub 2022 Dec 5.
Memory B cells (MBCs) generate rapid antibody responses upon secondary encounter with a pathogen. Here, we investigated the kinetics, avidity, and cross-reactivity of serum antibodies and MBCs in 155 SARS-CoV-2 infected and vaccinated individuals over a 16-month time frame. SARS-CoV-2-specific MBCs and serum antibodies reached steady-state titers with comparable kinetics in infected and vaccinated individuals. Whereas MBCs of infected individuals targeted both prefusion and postfusion Spike (S), most vaccine-elicited MBCs were specific for prefusion S, consistent with the use of prefusion-stabilized S in mRNA vaccines. Furthermore, a large fraction of MBCs recognizing postfusion S cross-reacted with human betacoronaviruses. The avidity of MBC-derived and serum antibodies increased over time resulting in enhanced resilience to viral escape by SARS-CoV-2 variants, including Omicron BA.1 and BA.2 sublineages, albeit only partially for BA.4 and BA.5 sublineages. Overall, the maturation of high-affinity and broadly reactive MBCs provides the basis for effective recall responses to future SARS-CoV-2 variants.
记忆B细胞（MBCs）在再次接触病原体时会产生快速的抗体反应。在此，我们在16个月的时间内，对155名感染和接种过SARS-CoV-2的个体的血清抗体和MBCs的动力学、亲和力和交叉反应性进行了研究。在感染和接种过疫苗的个体中，SARS-CoV-2特异性MBCs和血清抗体以相似的动力学达到稳态滴度。虽然感染个体的MBCs靶向融合前和融合后的刺突蛋白（S），但大多数疫苗诱导的MBCs对融合前S具有特异性，这与mRNA疫苗中使用融合前稳定化的S一致。此外，很大一部分识别融合后S的MBCs与人β冠状病毒发生交叉反应。MBC衍生抗体和血清抗体的亲和力随时间增加，从而增强了对包括奥密克戎BA.1和BA.2亚谱系在内的SARS-CoV-2变体病毒逃逸的抵抗力，尽管对BA.4和BA.5亚谱系只是部分有效。总体而言，高亲和力和广泛反应性MBCs的成熟为未来对SARS-CoV-2变体的有效回忆反应提供了基础。
