Messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective at inducing protective immunity. However, weak antibody responses are seen in some individuals, and cellular correlates of immunity remain poorly defined, especially for B cells. Here we used unbiased approaches to longitudinally dissect primary antibody, plasmablast, and memory B cell (MBC) responses to the two-dose mRNA-1273 vaccine in SARS-CoV-2–naive adults. Coordinated immunoglobulin A (IgA) and IgG antibody responses were preceded by bursts of spike-specific plasmablasts after both doses but earlier and more intensely after dose 2. While antibody and B cell cellular responses were generally robust, they also varied within the cohort and decreased over time after a dose-2 peak. Both antigen-nonspecific postvaccination plasmablast frequency after dose 1 and their spike-specific counterparts early after dose 2 correlated with subsequent antibody levels. This correlation between early plasmablasts and antibodies remained for titers measured at 6 months after vaccination. Several distinct antigen-specific MBC populations emerged postvaccination with varying kinetics, including two MBC populations that correlated with 2- and 6-month antibody titers. Both were IgG-expressing MBCs: one less mature, appearing as a correlate after the first dose, while the other MBC correlate showed a more mature and resting phenotype, emerging as a correlate later after dose 2. This latter MBC was also a major contributor to the sustained spike-specific MBC response observed at month 6. Thus, these plasmablasts and MBCs that emerged after both the first and second doses with distinct kinetics are potential determinants of the magnitude and durability of antibodies in response to mRNA-based vaccination.

中文翻译：

---

对 mRNA 疫苗接种产生一抗反应的早期人类 B 细胞特征

针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的信使 RNA (mRNA) 疫苗在诱导保护性免疫方面非常有效。然而，一些个体的抗体反应较弱，免疫的细胞相关性仍然不明确，尤其是 B 细胞。在这里，我们使用公正的方法纵向剖析首次接触 SARS-CoV-2 的成人对两剂 mRNA-1273 疫苗的一抗、浆母细胞和记忆 B 细胞 (MBC) 反应。两次剂量后，协调的免疫球蛋白 A (IgA) 和 IgG 抗体反应之前都会出现尖峰特异性浆母细胞的爆发，但在第 2 次剂量后更早且更强烈。虽然抗体和 B 细胞细胞反应通常很强劲，但它们在队列中也有所不同，并且下降随着时间的推移，剂量 2 峰值后。第 1 剂后的抗原非特异性疫苗接种后浆母细胞频率和第 2 剂后早期的尖峰特异性对应物频率均与随后的抗体水平相关。早期浆母细胞和抗体之间的这种相关性在疫苗接种后 6 个月时测量的滴度中仍然存在。疫苗接种后出现了几种不同的抗原特异性 MBC 群体，具有不同的动力学，包括与 2 个月和 6 个月抗体滴度相关的两个 MBC 群体。两者都是表达 IgG 的 MBC：一个不太成熟，在第一次剂量后出现相关性，而另一个 MBC 相关性显示出更成熟和静息表型，在第 2 次剂量后出现相关性。后一种 MBC 也是一个主要贡献者到第 6 个月观察到的持续尖峰特异性 MBC 反应。因此，在第一剂和第二剂后出现的这些浆母细胞和 MBC 具有不同的动力学，是响应基于 mRNA 的疫苗接种的抗体的强度和持久性的潜在决定因素。