Correlates of Neutralization against SARS-CoV-2 Variants of Concern by Early Pandemic Sera

• Published in: Journal of virology 2021-06, Vol.95 (14), p.e0040421-e0040421
• Main Authors: Vidal, Samuel J, Collier, Ai-Ris Y, Yu, Jingyou, McMahan, Katherine, Tostanoski, Lisa H, Ventura, John D, Aid, Malika, Peter, Lauren, Jacob-Dolan, Catherine, Anioke, Tochi, Chang, Aiquan, Wan, Huahua, Aguayo, Ricardo, Ngo, Debby, Gerszten, Robert E, Seaman, Michael S, Barouch, Dan H
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; COVID-19 - epidemiology; COVID-19 - immunology; Cross Reactions; Humans; Male; Pandemics; Pathogenesis and Immunity; SARS-CoV-2 - immunology
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/JVI.00404-21

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. 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.