2021-07-04

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Division of Infectious Diseases, Massachusetts General Hospital and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Program in Immunology, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.; Massachusetts Consortium on Pathogen Readiness, Boston, Massachusetts, USA.

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