Temporal associations of B and T cell immunity with robust vaccine responsiveness in a 16-week interval BNT162b2 regimen. Nayrac et al.

Spacing of the BNT162b2 mRNA doses beyond 3 weeks raised concerns about vaccine efficacy. We longitudinally analyzed B cell, T cell and humoral responses to two BNT162b2 mRNA doses administered 16 weeks apart in 53 SARS-CoV-2 naïve and previously-infected donors. This regimen elicited robust RBD-specific B cell responses whose kinetics differed between cohorts, the second dose leading to increased magnitude in naïve participants only. While boosting did not increase magnitude of CD4+ T cell responses further compared to the first dose, unsupervised clustering of single-cell features revealed phenotypic and functional shifts over time and between cohorts. Integrated analysis showed longitudinal immune component-specific associations, with early Thelper responses post-first dose correlating with B cell responses after the second dose, and memory Thelper generated between doses correlating with CD8 T cell responses after boosting. Therefore, boosting elicits a robust cellular recall response after the 16-week interval, indicating functional immune memory.将BNT162b2 mRNA疫苗的接种间隔延长至3周以上，曾引发学界对疫苗防护效力的担忧。本研究对53名新冠病毒（SARS-CoV-2）初治及既往感染受试者展开纵向分析，评估其在间隔16周接种两剂BNT162b2 mRNA疫苗后的B细胞、T细胞与体液免疫应答情况。该免疫方案可诱导强烈的受体结合域（Receptor Binding Domain, RBD）特异性B细胞应答，且应答动力学特征在不同队列间存在差异；仅新冠初治受试者在接种第二剂后，其B细胞应答强度得到显著提升。尽管与首剂接种相比，加强接种未能进一步提升CD4+ T细胞应答的强度，但对单细胞特征的无监督聚类分析显示，不同时间点及不同队列间的细胞表型与功能均发生了显著改变。整合分析揭示了纵向免疫组分间的特异性关联：首剂接种后早期的辅助性T细胞（Thelper）应答与第二剂接种后的B细胞应答相关，而两剂接种间期产生的记忆性辅助性T细胞与加强接种后的CD8+ T细胞应答存在显著相关性。综上，在16周间隔后实施加强接种可诱导强烈的细胞回忆应答，证实了功能性免疫记忆的存在。