ABSTRACT 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.
【저자키워드】 SARS-CoV-2, Neutralizing antibodies, T cells, 【초록키워드】 neutralizing antibody, antibodies, pandemic, Mutation, Immunity, Vaccines, B.1.351, neutralization, susceptibility, COVID-19 pandemic, variant, SARS-CoV-2 variant, Infection, variants, Receptor binding domain, Cohort, T cell, SARS-CoV-2 variants, spike gene, B.1.1.7, RBD, immune responses, response, T cell responses, cross-neutralization, NTD, convalescent, natural infection, homologous, Critical, clinical feature, mechanism, binding, N-terminal domain, Evidence, natural immunity, Vaccine-induced immunity, Virological, B.1.351 variant, These data, nAb response, NAb responses, primary mechanism, NAb titers, immunological, effective, stimulated, significantly, investigated, reduced, characterized, subjects, overcome, promote, reduction in, Increasing, exacerbate, COVID-19 convalescent patient, 【제목키워드】 concern,