mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
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DOI：
10.1101/2021.01.15.426911
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发表时间：
2021-02-10
期刊：
影响因子：
64.8
通讯作者：
Nussenzweig, Michel C.
中科院分区：
文献类型：
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作者：
Wang, Zijun;Schmidt, Fabian;Nussenzweig, Michel C.
在这里，我们报告了一组20名志愿者的抗体和记忆B细胞反应，他们接受了Moderna（mRNA-1273）或Pfizer-BioNTech（BNT 162 b2）疫苗抗SARS-CoV-2（1-4）。第二次注射疫苗后8周，志愿者显示出高水平的IgM和IgG抗SARS-CoV-2刺突蛋白（S）和受体结合域（RBD）结合滴度。此外，接种疫苗的志愿者的血浆中和活性和RBD特异性记忆B细胞的相对数量与自然感染恢复的个体相当（5，6）。然而，针对编码E484 K-、N501 Y-或K417 N/E484 K/N501-突变S的SARS-CoV-2变体的活性降低了一个小但显著的幅度。由疫苗引发的单克隆抗体有效地中和SARS-CoV-2，并靶向许多不同的RBD表位，这些表位与从受感染供体分离的单克隆抗体相同（5-8）。然而，我们测试的17种最有效的单克隆抗体中有14种的中和作用被K417 N、E484 K或N501 Y突变降低或消除。值得注意的是，当我们在疫苗诱导的单克隆抗体存在下培养表达SARS-CoV-2 S的重组水泡性口炎病毒时，这些突变被选择。总之，这些结果表明，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mRNA疫苗可能需要定期更新，以避免潜在的临床疗效损失。
Here we report on the antibody and memory B cell responses of a cohort of 20 volunteers who received the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccine against SARS-CoV-2(1-4). Eight weeks after the second injection of vaccine, volunteers showed high levels of IgM and IgG anti-SARS-CoV-2 spike protein (S) and receptor-binding-domain (RBD) binding titre. Moreover, the plasma neutralizing activity and relative numbers of RBD-specific memory B cells of vaccinated volunteers were equivalent to those of individuals who had recovered from natural infection(5,6). However, activity against SARS-CoV-2 variants that encode E484K-, N501Y- or K417N/E484K/N501-mutant S was reduced by a small-but significant-margin. The monoclonal antibodies elicited by the vaccines potently neutralize SARS-CoV-2, and target a number of different RBD epitopes in common with monoclonal antibodies isolated from infected donors(5-8). However, neutralization by 14 of the 17 most-potent monoclonal antibodies that we tested was reduced or abolished by the K417N, E484K or N501Y mutation. Notably, these mutations were selected when we cultured recombinant vesicular stomatitis virus expressing SARS-CoV-2 S in the presence of the monoclonal antibodies elicited by the vaccines. Together, these 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 a potential loss of clinical efficacy.