Evolution of antibody immunity to SARS-CoV-2.

TitleEvolution of antibody immunity to SARS-CoV-2.
Publication TypeJournal Article
Year of Publication2021
AuthorsGaebler C, Wang Z, Lorenzi JCC, Muecksch F, Finkin S, Tokuyama M, Cho A, Jankovic M, Schaefer-Babajew D, Oliveira TY, Cipolla M, Viant C, Barnes CO, Bram Y, Breton G, Hägglöf T, Mendoza P, Hurley A, Turroja M, Gordon K, Millard KG, Ramos V, Schmidt F, Weisblum Y, Jha D, Tankelevich M, Martinez-Delgado G, Yee J, Patel R, Dizon J, Unson-O'Brien C, Shimeliovich I, Robbiani DF, Zhao Z, Gazumyan A, Schwartz RE, Hatziioannou T, Bjorkman PJ, Mehandru S, Bieniasz PD, Caskey M, Nussenzweig MC
JournalNature
Volume591
Issue7851
Pagination639-644
Date Published2021 03
ISSN1476-4687
KeywordsAdolescent, Adult, Aged, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Antigens, Viral, B-Lymphocytes, Biopsy, Cohort Studies, COVID-19, Fluorescent Antibody Technique, Humans, Immunity, Humoral, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Immunologic Memory, Intestines, Middle Aged, Mutation, SARS-CoV-2, Somatic Hypermutation, Immunoglobulin, Spike Glycoprotein, Coronavirus, Time Factors, Young Adult
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 models. 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.

DOI10.1038/s41586-021-03207-w
Alternate JournalNature
PubMed ID33461210
PubMed Central IDPMC8221082
Grant ListR01 AI078788 / AI / NIAID NIH HHS / United States
P01 AI138938 / AI / NIAID NIH HHS / United States
R01 CA234614 / CA / NCI NIH HHS / United States
R01 DK120035 / DK / NIDDK NIH HHS / United States
R03 DK117252 / DK / NIDDK NIH HHS / United States
R37 AI064003 / AI / NIAID NIH HHS / United States
P50 AI150464 / AI / NIAID NIH HHS / United States
R01 AI107301 / AI / NIAID NIH HHS / United States
/ WT_ / Wellcome Trust / United Kingdom
R01 DK123749 / DK / NIDDK NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States
UL1 TR001866 / TR / NCATS NIH HHS / United States
R01 DK121072 / DK / NIDDK NIH HHS / United States
U19 AI111825 / AI / NIAID NIH HHS / United States
Related Faculty: 
Zhen Zhao, Ph.D.

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