The deployment of effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to eradicate the coronavirus disease 2019 (COVID-19) pandemic. Many licensed vaccines confer protection by inducing long-lived plasma cells (LLPCs) and memory B cells (MBCs), cell types canonically generated during germinal center (GC) reactions. Here, we directly compared two vaccine platforms—mRNA vaccines and a recombinant protein formulated with an MF59-like adjuvant—looking for their abilities to quantitatively and qualitatively shape SARS-CoV-2-specific primary GC responses over time. We demonstrated that a single immunization with SARS-CoV-2 mRNA, but not with the recombinant protein vaccine, elicited potent SARS-CoV-2-specific GC B and T follicular helper (Tfh) cell responses as well as LLPCs and MBCs. Importantly, GC responses strongly correlated with neutralizing antibody production. mRNA vaccines more efficiently induced key regulators of the Tfh cell program and influenced the functional properties of Tfh cells. Overall, this study identifies SARS-CoV-2 mRNA vaccines as strong candidates for promoting robust GC-derived immune responses.

部署针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的有效疫苗对于根除 2019 年冠状病毒病 (COVID-19) 大流行至关重要。许多获得许可的疫苗通过诱导长寿命浆细胞 (LLPC) 和记忆 B 细胞 (MBC) 来提供保护，这些细胞类型是在生发中心 (GC) 反应过程中典型产生的。在这里，我们直接比较了两种疫苗平台——mRNA疫苗和用类MF59佐剂配制的重组蛋白——寻找它们随着时间的推移定量和定性塑造SARS-CoV-2特异性初级GC反应的能力。我们证明，使用 SARS-CoV-2 mRNA（而非重组蛋白疫苗）进行单次免疫可引发有效的 SARS-CoV-2 特异性 GC B 和滤泡辅助性 T (Tfh) 细胞反应以及 LLPC 和 MBC。重要的是，GC 反应与中和抗体的产生密切相关。mRNA 疫苗更有效地诱导 Tfh 细胞程序的关键调节因子并影响 Tfh 细胞的功能特性。总体而言，这项研究将 SARS-CoV-2 mRNA 疫苗确定为促进强有力的 GC 衍生免疫反应的有力候选疫苗。