Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity

Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity
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DOI:
10.1101/2021.02.14.21251704
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发表时间:
2021-04-29
期刊:
影响因子:
64.5
通讯作者:
Balazs, Alejandro B.
Balazs, Alejandro B.
中科院分区:
生物学1区
文献类型:
--
作者:
Garcia-Beltran, Wilfredo F.;Lam, Evan C.;Balazs, Alejandro B.

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疫苗接种可增强免疫应答,有效中和SARS-CoV-2。然而,正在进行的监测显示,出现了含有中和抗体主要靶点spike突变的变体。为了了解这些变异的影响,我们评估了99名接受一剂或两剂BNT 162 b2或mRNA-1273疫苗的个体对代表10种全球流行的SARS-CoV-2假病毒的中和效力。10种假病毒中有5种携带受体结合结构域突变,包括K417 N/T、E484 K和N501 Y,对中和具有高度抗性。B.1.351变异体的交叉中和与SARS-CoV和蝙蝠来源的WIV 1-CoV相当,表明相对少量的突变可以介导疫苗应答的有效逃逸。虽然中和耐药的临床影响仍不确定,但这些结果强调了变异体逃避中和体液免疫的可能性,并强调需要针对不断演变的大流行制定广泛的保护性干预措施。
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 receptorbinding 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.