Evolution of antibody immunity to SARS-CoV-2.

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 the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection 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 with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. 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.

• Authors: Christian Gaebler, Zijun Wang, Julio C C Lorenzi, Frauke Muecksch, Shlomo Finkin, Minami Tokuyama, Alice Cho, Mila Jankovic, Dennis Schaefer-Babajew, Thiago Y Oliveira, Melissa Cipolla, Charlotte Viant, Christopher O Barnes, Yaron Bram, Gaëlle Breton, Thomas Hägglöf, Pilar Mendoza, Arlene Hurley, Martina Turroja, Kristie Gordon, Katrina G Millard, Victor Ramos, Fabian Schmidt, Yiska Weisblum, Divya Jha, Michael Tankelevich, Gustavo Martinez-Delgado, Jim Yee, Roshni Patel, Juan Dizon, Cecille Unson-O'Brien, Irina Shimeliovich, Davide F Robbiani, Zhen Zhao, Anna Gazumyan, Robert E Schwartz, Theodora Hatziioannou, Pamela J Bjorkman, Saurabh Mehandru, Paul D Bieniasz, Marina Caskey, Michel C Nussenzweig
• Journal: Nature (Nature) Vol. 591 Issue 7851 Pg. 639-644 (03 2021) ISSN: 1476-4687 [Electronic] England
• PMID: 33461210 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Antibodies, Viral
• Antigens, Viral
• Immunoglobulin A
• Immunoglobulin G
• Immunoglobulin M
• Spike Glycoprotein, Coronavirus
• spike protein, SARS-CoV-2

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal (blood, immunology)
• Antibodies, Neutralizing (blood, genetics, immunology)
• Antibodies, Viral (blood, genetics, immunology)
• Antigens, Viral (chemistry, genetics, immunology)
• B-Lymphocytes (cytology, immunology)
• Biopsy
• COVID-19 (blood, immunology)
• Cohort Studies
• Fluorescent Antibody Technique
• Humans
• Immunity, Humoral (genetics, immunology)
• Immunoglobulin A (immunology)
• Immunoglobulin G (immunology)
• Immunoglobulin M (immunology)
• Immunologic Memory (immunology)
• Intestines (immunology)
• Middle Aged
• Mutation
• SARS-CoV-2 (immunology)
• Somatic Hypermutation, Immunoglobulin
• Spike Glycoprotein, Coronavirus (chemistry, genetics, immunology)
• Time Factors
• Young Adult