RT Journal Article SR Electronic T1 Evolution of Antibody Immunity to SARS-CoV-2 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.11.03.367391 DO 10.1101/2020.11.03.367391 A1 Christian Gaebler A1 Zijun Wang A1 Julio C. C. Lorenzi A1 Frauke Muecksch A1 Shlomo Finkin A1 Minami Tokuyama A1 Alice Cho A1 Mila Jankovic A1 Dennis Schaefer-Babajew A1 Thiago Y. Oliveira A1 Melissa Cipolla A1 Charlotte Viant A1 Christopher O. Barnes A1 Yaron Bram A1 Gaëlle Breton A1 Thomas Hägglöf A1 Pilar Mendoza A1 Arlene Hurley A1 Martina Turroja A1 Kristie Gordon A1 Katrina G. Millard A1 Victor Ramos A1 Fabian Schmidt A1 Yiska Weisblum A1 Divya Jha A1 Michael Tankelevich A1 Gustavo Martinez-Delgado A1 Jim Yee A1 Roshni Patel A1 Juan Dizon A1 Cecille Unson-O’Brien A1 Irina Shimeliovich A1 Davide F. Robbiani A1 Zhen Zhao A1 Anna Gazumyan A1 Robert E. Schwartz A1 Theodora Hatziioannou A1 Pamela J. Bjorkman A1 Saurabh Mehandru A1 Paul D. Bieniasz A1 Marina Caskey A1 Michel C. Nussenzweig YR 2021 UL http://biorxiv.org/content/early/2021/01/04/2020.11.03.367391.abstract AB Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with development of variable levels of antibodies with neutralizing activity that can protect against infection in animal models. Antibody levels decrease with time, but the nature and quality of the memory B cells that would be called upon to produce antibodies upon re-infection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection. We find that IgM, and IgG anti-SARS-CoV-2 spike protein receptor binding domain (RBD) antibody titers decrease significantly with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by five-fold in pseudotype virus assays. In contrast, the number of RBD-specific memory B cells is unchanged. Memory B cells display clonal turnover after 6.2 months, and the antibodies they express have greater somatic hypermutation, increased potency and resistance to RBD mutations, indicative of continued evolution of the humoral response. Analysis of intestinal biopsies obtained from asymptomatic individuals 4 months after coronavirus disease-2019 (COVID-19) onset, using immunofluorescence, or polymerase chain reaction, revealed persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 volunteers. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.Competing Interest StatementThe Rockefeller University has filed a provisional patent application in connection with this work on which D.F.R. and M.C.N. are inventors (US patent 63/021,387).