Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Cell. 2021 Apr 29;184(9):2372-2383.e9. doi: 10.1016/j.cell.2021.03.013. Epub 2021 Mar 12.
Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.
接种疫苗可引发能够有效中和 SARS-CoV-2 的免疫反应。然而，持续监测发现，出现了携带刺突蛋白突变的变异株，刺突蛋白是中和抗体的主要靶标。为了了解这些变异株的影响，我们评估了 99 名个体对代表 10 种全球流行 SARS-CoV-2 株的假病毒的中和效力，这些个体接受了一剂或两剂 BNT162b2 或 mRNA-1273 疫苗。其中 5 种假病毒，包括 K417N/T、E484K 和 N501Y 在内的受体结合域突变，对中和作用具有高度抗性。对 B.1.351 变异株的交叉中和作用与 SARS-CoV 和源自蝙蝠的 WIV1-CoV 相当，表明相对较少的突变可介导对疫苗反应的有效逃逸。虽然中和耐药性的临床影响尚不确定，但这些结果突出了变异株逃避中和体液免疫的潜力，并强调需要开发广泛的保护干预措施来应对不断演变的大流行。
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