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mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
Nature ( IF 64.8 ) Pub Date : 2021-02-10 , DOI: 10.1038/s41586-021-03324-6
Zijun Wang 1 , Fabian Schmidt 2 , Yiska Weisblum 2 , Frauke Muecksch 2 , Christopher O Barnes 3 , Shlomo Finkin 1 , Dennis Schaefer-Babajew 1 , Melissa Cipolla 1 , Christian Gaebler 1 , Jenna A Lieberman 4 , Thiago Y Oliveira 1 , Zhi Yang 3 , Morgan E Abernathy 3 , Kathryn E Huey-Tubman 3 , Arlene Hurley 5 , Martina Turroja 1 , Kamille A West 6 , Kristie Gordon 1 , Katrina G Millard 1 , Victor Ramos 1 , Justin Da Silva 2 , Jianliang Xu 4 , Robert A Colbert 7 , Roshni Patel 1 , Juan Dizon 1 , Cecille Unson-O'Brien 1 , Irina Shimeliovich 1 , Anna Gazumyan 1 , Marina Caskey 1 , Pamela J Bjorkman 3 , Rafael Casellas 4, 8 , Theodora Hatziioannou 2 , Paul D Bieniasz 2, 9 , Michel C Nussenzweig 1, 9
Affiliation  

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-21,2,3,4. 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 infection5,6. 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 donors5,6,7,8. 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.



中文翻译:

mRNA 疫苗引发针对 SARS-CoV-2 和循环变异体的抗体

在此,我们报告了 20 名志愿者接受了针对 SARS-CoV-2 1,2,3,4疫苗的 Moderna (mRNA-1273) 或辉瑞 BioNTech (BNT162b2) 疫苗的抗体和记忆 B 细胞反应。第二次注射疫苗八周后,志愿者表现出高水平的 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 细胞的相对数量与从自然感染中恢复的个体相当5,6。然而,针对编码 E484K、N501Y 或 K417N/E484K/N501 突变体 S 的 SARS-CoV-2 变体的活性略有降低,但幅度很大。疫苗产生的单克隆抗体可有效中和 SARS-CoV-2,并针对许多不同的 RBD 表位,这些表位与从受感染的供体中分离的单克隆抗体相同5,6,7,8。然而,我们测试的 17 种最有效的单克隆抗体中有 14 种的中和作用因 K417N、E484K 或 N501Y 突变而减少或消除。值得注意的是,当我们在疫苗引发的单克隆抗体存在的情况下培养表达 SARS-CoV-2 S 的重组水泡性口炎病毒时,选择了这些突变。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。

更新日期:2021-02-10
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