Correlates of Neutralization against SARS-CoV-2 Variants of Concern by Early Pandemic Sera.
Correlates of Neutralization against SARS-CoV-2 Variants of Concern by Early Pandemic Sera.
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早期大流行血清对SARS-CoV-2变异株中和作用的相关性
DOI：
10.1128/jvi.00404-21
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发表时间：
2021-06-24
影响因子：
5.4
通讯作者：
Barouch DH
中科院分区：
文献类型：
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作者：
Vidal SJ;Collier AY;Yu J;McMahan K;Tostanoski LH;Ventura JD;Aid M;Peter L;Jacob-Dolan C;Anioke T;Chang A;Wan H;Aguayo R;Ngo D;Gerszten RE;Seaman MS;Barouch DH
克服自然免疫和疫苗诱导免疫的新出现的令人关注的SARS-CoV-2变体有可能加剧COVID-19大流行。越来越多的证据表明，中和抗体（NAb）反应是预防感染的主要机制。然而，在COVID-19早期大流行期间获得的自然免疫在多大程度上和机制上赋予新出现的变体交叉中和作用，人们知之甚少。在这项研究中，我们在一个特征明确的大流行早期恢复期受试者队列中调查了B.1.1.7和B.1.351 SARS-CoV-2变体的交叉中和作用。我们观察到B.1.1.7的交叉中和略有下降，但B.1.351的交叉中和大幅减少了4.8倍。交叉中和的相关因素包括受体结合域（RBD）和n端结构域（NTD）结合抗体、同源NAb滴度和膜定向T细胞反应。这些数据阐明了大流行早期恢复期免疫反应对新发变异的交叉中和作用。对SARS-CoV-2的广泛免疫对于结束COVID-19大流行是必要的。NAb反应是免疫的一个重要组成部分，可由自然感染和疫苗刺激。然而，正在出现的SARS-CoV-2变体包含刺突基因突变，可促进逃避NAb反应。因此，这些变异可能会延迟COVID-19大流行的控制。我们研究了COVID-19早期恢复期患者的NAb应答是否对B.1.1.7和B.1.351两种SARS-CoV-2变体有效。我们观察到B.1.351变异对早期大流行NAb反应的易感性显著降低。我们还描述了与交叉中和相关的病毒学、免疫学和临床特征。这些研究增加了我们对新出现的SARS-CoV-2变体的理解。
Emerging SARS-CoV-2 variants of concern that overcome natural and vaccine-induced immunity threaten to exacerbate the COVID-19 pandemic. Increasing evidence suggests that neutralizing antibody (NAb) responses are a primary mechanism of protection against infection. However, little is known about the extent and mechanisms by which natural immunity acquired during the early COVID-19 pandemic confers cross-neutralization of emerging variants. In this study, we investigated cross-neutralization of the B.1.1.7 and B.1.351 SARS-CoV-2 variants in a well-characterized cohort of early pandemic convalescent subjects. We observed modestly decreased cross-neutralization of B.1.1.7 but a substantial 4.8-fold reduction in cross-neutralization of B.1.351. Correlates of cross-neutralization included receptor binding domain (RBD) and N-terminal domain (NTD) binding antibodies, homologous NAb titers, and membrane-directed T cell responses. These data shed light on the cross-neutralization of emerging variants by early pandemic convalescent immune responses. IMPORTANCE Widespread immunity to SARS-CoV-2 will be necessary to end the COVID-19 pandemic. NAb responses are a critical component of immunity that can be stimulated by natural infection as well as vaccines. However, SARS-CoV-2 variants are emerging that contain mutations in the spike gene that promote evasion from NAb responses. These variants may therefore delay control of the COVID-19 pandemic. We studied whether NAb responses from early COVID-19 convalescent patients are effective against the two SARS-CoV-2 variants, B.1.1.7 and B.1.351. We observed that the B.1.351 variant demonstrates significantly reduced susceptibility to early pandemic NAb responses. We additionally characterized virological, immunological, and clinical features that correlate with cross-neutralization. These studies increase our understanding of emerging SARS-CoV-2 variants.