Wang Zijun, Schmidt Fabian, Weisblum Yiska, Muecksch Frauke, Barnes Christopher O, Finkin Shlomo, Schaefer-Babajew Dennis, Cipolla Melissa, Gaebler Christian, Lieberman Jenna A, Oliveira Thiago Y, Yang Zhi, Abernathy Morgan E, Huey-Tubman Kathryn E, Hurley Arlene, Turroja Martina, West Kamille A, Gordon Kristie, Millard Katrina G, Ramos Victor, Da Silva Justin, Xu Jianliang, Colbert Robert A, Patel Roshni, Dizon Juan, Unson-O'Brien Cecille, Shimeliovich Irina, Gazumyan Anna, Caskey Marina, Bjorkman Pamela J, Casellas Rafael, Hatziioannou Theodora, Bieniasz Paul D, Nussenzweig Michel C
bioRxiv. 2021 Jan 30:2021.01.15.426911. doi: 10.1101/2021.01.15.426911.
To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 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) and 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 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.
截至目前，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）已感染超过1亿人，导致200多万人死亡。许多疫苗正在被用于预防2019冠状病毒病（COVID-19），包括两种新型的基于信使核糖核酸（mRNA）的疫苗。这些疫苗能引发中和抗体，且似乎安全有效，但所引发抗体的确切性质尚不清楚。在此，我们报告了20名志愿者接种Moderna（mRNA-1273）或辉瑞-生物科技（BNT162b2）疫苗后的抗体和记忆B细胞反应。与先前的报告一致，第二次疫苗注射8周后，志愿者体内显示出高水平的IgM以及抗SARS-CoV-2刺突蛋白（S）和受体结合域（RBD）的IgG结合滴度。此外，血浆中和活性以及RBD特异性记忆B细胞的相对数量与从自然感染中康复的个体相当。然而，针对编码E484K或N501Y或K417N:E484K:N501Y组合的SARS-CoV-2变体的活性有小幅但显著的降低。与这些发现一致，疫苗引发的单克隆抗体（mAb）能有效中和SARS-CoV-2，靶向许多与从感染供体中分离出的mAb共有的不同RBD表位。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，所测试的17种最有效的mAb中有14种的中和作用因K417N、E484K或N501Y突变而降低或消除。值得注意的是，当重组水疱性口炎病毒（rVSV）/SARS-CoV-2 S在疫苗引发的mAb存在下培养时，会选择相同的突变。综合来看，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丧失。
