Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape.
Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape.
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SARS-CoV-2 Spike 特异性记忆 B 细胞的成熟可增强病毒逃逸的能力。
DOI：
10.1101/2022.09.30.509852
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
McCallum,Matthew
中科院分区：
文献类型：
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作者：
Marzi,Roberta;Bassi,Jessica;Silacci-Fregni,Chiara;Bartha,Istvan;Muoio,Francesco;Culap,Katja;Sprugasci,Nicole;Lombardo,Gloria;Saliba,Christian;Cameroni,Elisabetta;Cassotta,Antonino;Low,JunSiong;Walls,AlexandraC;McCallum,Matthew
记忆B细胞（MBC）在与病原体二次相遇时产生快速抗体应答。在这里，我们研究了155个SARS-CoV-2感染和接种疫苗的个体在16个月的时间范围内血清抗体和MBC的动力学，亲合力和交叉反应性。SARS-CoV-2特异性MBC和血清抗体在感染和接种个体中达到稳态滴度，具有可比的动力学。尽管感染个体的MBC靶向融合前和融合后刺突（S），但大多数疫苗诱导的MBC对融合前S具有特异性，这与mRNA疫苗中融合前稳定的S的使用一致。此外，大部分识别融合后S的MBC与人β冠状病毒发生交叉反应。MBC衍生的抗体和血清抗体的亲合力随时间增加，导致对SARS-CoV-2变体的病毒逃逸的弹性增强，包括Omicron BA.1和BA.2亚系，尽管仅部分用于BA.4和BA.5亚系。总的来说，高亲和力和广泛反应性MBC的成熟为未来SARS-CoV-2变体的有效回忆反应提供了基础。
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.