PT  - JOURNAL ARTICLE
AU  - Christian Gaebler
AU  - Zijun Wang
AU  - Julio C. C. Lorenzi
AU  - Frauke Muecksch
AU  - Shlomo Finkin
AU  - Minami Tokuyama
AU  - Mark Ladinsky
AU  - Alice Cho
AU  - Mila Jankovic
AU  - Dennis Schaefer-Babajew
AU  - Thiago Y. Oliveira
AU  - Melissa Cipolla
AU  - Charlotte Viant
AU  - Christopher O. Barnes
AU  - Arlene Hurley
AU  - Martina Turroja
AU  - Kristie Gordon
AU  - Katrina G. Millard
AU  - Victor Ramos
AU  - Fabian Schmidt
AU  - Yiska Weisblum
AU  - Divya Jha
AU  - Michael Tankelevich
AU  - Jim Yee
AU  - Irina Shimeliovich
AU  - Davide F. Robbiani
AU  - Zhen Zhao
AU  - Anna Gazumyan
AU  - Theodora Hatziioannou
AU  - Pamela J. Bjorkman
AU  - Saurabh Mehandru
AU  - Paul D. Bieniasz
AU  - Marina Caskey
AU  - Michel C. Nussenzweig
TI  - Evolution of Antibody Immunity to SARS-CoV-2
AID  - 10.1101/2020.11.03.367391
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.03.367391
4099  - http://biorxiv.org/content/early/2020/11/05/2020.11.03.367391.short
4100  - http://biorxiv.org/content/early/2020/11/05/2020.11.03.367391.full
AB  - SARS-CoV-2 has infected 47 million individuals and is responsible for over 1.2 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 3 months after COVID-19 onset, using immunofluorescence, electron tomography or polymerase chain reaction, revealed persistence of SARS-CoV-2 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).