@article {Gaebler2020.11.03.367391, author = {Christian Gaebler and Zijun Wang and Julio C. C. Lorenzi and Frauke Muecksch and Shlomo Finkin and Minami Tokuyama and Alice Cho and Mila Jankovic and Dennis Schaefer-Babajew and Thiago Y. Oliveira and Melissa Cipolla and Charlotte Viant and Christopher O. Barnes and Yaron Bram and Ga{\"e}lle Breton and Thomas H{\"a}ggl{\"o}f and Pilar Mendoza and Arlene Hurley and Martina Turroja and Kristie Gordon and Katrina G. Millard and Victor Ramos and Fabian Schmidt and Yiska Weisblum and Divya Jha and Michael Tankelevich and Gustavo Martinez-Delgado and Jim Yee and Roshni Patel and Juan Dizon and Cecille Unson-O{\textquoteright}Brien and Irina Shimeliovich and Davide F. Robbiani and Zhen Zhao and Anna Gazumyan and Robert E. Schwartz and Theodora Hatziioannou and Pamela J. Bjorkman and Saurabh Mehandru and Paul D. Bieniasz and Marina Caskey and Michel C. Nussenzweig}, title = {Evolution of Antibody Immunity to SARS-CoV-2}, elocation-id = {2020.11.03.367391}, year = {2021}, doi = {10.1101/2020.11.03.367391}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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).}, URL = {https://www.biorxiv.org/content/early/2021/01/04/2020.11.03.367391}, eprint = {https://www.biorxiv.org/content/early/2021/01/04/2020.11.03.367391.full.pdf}, journal = {bioRxiv} }