To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected nearly 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease-2019 (COVID-19) including two novel mRNA-based vaccines. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S), receptor binding domain (RBD) binding titers. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

中文翻译：

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mRNA 疫苗引发的针对 SARS-CoV-2 和循环变体的抗体

迄今为止，严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 已感染近 1 亿人，导致超过 200 万人死亡。正在部署许多疫苗来预防 2019 年冠状病毒病 (COVID-19)，其中包括两种基于 mRNA 的新型疫苗。这些疫苗会引发中和抗体，似乎是安全有效的，但引发抗体的确切性质尚不清楚。在这里，我们报告了接受 Moderna (mRNA-1273) 或 Pfizer-BioNTech (BNT162b2) 疫苗的 20 名志愿者的抗体和记忆 B 细胞反应。与之前的报道一致，在第二次疫苗注射后 8 周，志愿者显示出高水平的 IgM、IgG 抗 SARS-CoV-2 刺突蛋白 (S)、受体结合域 (RBD) 结合滴度。此外，等离子体中和活性，并且RBD特异性记忆B细胞的相对数量与从自然感染中恢复的个体相当。然而，针对编码 E484K 或 N501Y 或 K417N:E484K:N501Y 组合的 SARS-CoV-2 变体的活性降低了小幅但显着的幅度。与这些发现一致，疫苗引发的单克隆抗体 (mAb) 可有效中和 SARS-CoV-2，靶向许多不同的 RBD 表位，这些表位与从受感染供体分离的 mAb 相同。与 S 三聚体复合的 mAb 的结构分析表明，疫苗和病毒编码的 S 采用相似的构象来诱导等效的抗 RBD 抗体。然而，K417N、E484K 或 N501Y 突变降低或消除了 17 种最有效 mAb 中的 14 种的中和作用。尤其，当在疫苗引发的 mAb 存在下培养重组水泡性口炎病毒 (rVSV)/SARS-CoV-2 S 时，选择了相同的突变。综合结果表明，临床使用的单克隆抗体应针对新出现的变体进行测试，并且可能需要定期更新 mRNA 疫苗以避免潜在的临床疗效损失。