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

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

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 cross-neutralization of emerging variants by early pandemic convalescent immune responses.IMPORTANCEWidespread immunity to SARS-CoV-2 will be necessary to end the COVID-19 pandemic. Neutralizing antibody (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 virologic, immunologic, and clinical features that correlate with cross-neutralization. These studies increase our understanding of emerging SARS-CoV-2 variants.