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：
10.1016/j.cell.2021.03.013
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发表时间：
2021-04-29
期刊：
影响因子：
64.5
通讯作者：
Balazs AB
中科院分区：
文献类型：
--
作者：
Garcia-Beltran WF;Lam EC;St Denis K;Nitido AD;Garcia ZH;Hauser BM;Feldman J;Pavlovic MN;Gregory DJ;Poznansky MC;Sigal A;Schmidt AG;Iafrate AJ;Naranbhai V;Balazs AB
接种疫苗可产生能够有效中和SARS-CoV-2的免疫反应。然而，正在进行的监测发现，在中和抗体的主要目标SPEKE中出现了含有突变的变体。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BNT162b2或mRNA-1273疫苗的人对代表10种全球流行的SARS-CoV-2伪病毒的中和效力。在10个含有受体结合区突变的伪病毒中，有5个病毒，包括K417N/T、E484K和N501Y，高度抵抗中和。B.1.351变异体的交叉中和作用与SARS-CoV和BAT衍生的WIV1-CoV相似，表明相对较少的突变可以介导有效的疫苗逃逸。虽然中和耐药性的临床影响仍不确定，但这些结果突显了变异株逃避中和体液免疫的可能性，并强调需要制定广泛的保护性干预措施，以应对不断演变的大流行。在全球范围内已经出现了大量含有SARS-CoV-2基因突变的变异株，该疫苗对同源假病毒具有很强的中和活性。具有受体结合域(RBD)突变的菌株的交叉中和能力很差，RBD和非RBD突变都介导了逃避疫苗诱导的体液免疫。对接种一剂或两剂SARS-CoV-2 10个循环变异株的个体血清的分析表明，尤其是P.1和B.1.351表现出有限的疫苗诱导的体液免疫中和作用。这种逃避被发现在很大程度上是由SARS-CoV-2尖峰的受体结合域的突变所介导的。
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. Numerous variants of SARS-CoV-2-harboring mutations in spike have arisen globally mRNA vaccines elicit potent neutralizing activity against homologous pseudovirus Cross-neutralization of strains with receptor-binding domain (RBD) mutations is poor Both RBD and non-RBD mutations mediate escape from vaccine-induced humoral immunity Analyses of sera from individuals vaccinated with one or two doses of mRNA vaccines against 10 circulating variants of SARS-CoV-2 show that P.1 and B.1.351 in particular exhibit limited neutralization by vaccine-induced humoral immunity. This escape was found to be largely mediated by mutations in the receptor-binding domain of SARS-CoV-2 spike.
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