tetano
Editor, Senior Moderator
Nature
. 2021 Jan 18.
doi: 10.1038/s41586-021-03207-w. Online ahead of print.
Evolution of antibody immunity to SARS-CoV-2
Christian Gaebler[SUP] #[/SUP][SUP] 1 [/SUP], Zijun Wang[SUP] #[/SUP][SUP] 1 [/SUP], Julio C C Lorenzi[SUP] #[/SUP][SUP] 1 [/SUP], Frauke Muecksch[SUP] #[/SUP][SUP] 2 [/SUP], Shlomo Finkin[SUP] #[/SUP][SUP] 1 [/SUP], Minami Tokuyama[SUP] #[/SUP][SUP] 3 [/SUP], Alice Cho[SUP] #[/SUP][SUP] 1 [/SUP], Mila Jankovic[SUP] #[/SUP][SUP] 1 [/SUP], Dennis Schaefer-Babajew[SUP] #[/SUP][SUP] 1 [/SUP], Thiago Y Oliveira[SUP] #[/SUP][SUP] 1 [/SUP], Melissa Cipolla[SUP] #[/SUP][SUP] 1 [/SUP], Charlotte Viant[SUP] 1 [/SUP], Christopher O Barnes[SUP] 4 [/SUP], Yaron Bram[SUP] 5 [/SUP], Ga?lle Breton[SUP] 1 [/SUP], Thomas H?ggl?f[SUP] 1 [/SUP], Pilar Mendoza[SUP] 1 [/SUP], Arlene Hurley[SUP] 6 [/SUP], Martina Turroja[SUP] 1 [/SUP], Kristie Gordon[SUP] 1 [/SUP], Katrina G Millard[SUP] 1 [/SUP], Victor Ramos[SUP] 1 [/SUP], Fabian Schmidt[SUP] 2 [/SUP], Yiska Weisblum[SUP] 2 [/SUP], Divya Jha[SUP] 3 [/SUP], Michael Tankelevich[SUP] 3 [/SUP], Gustavo Martinez-Delgado[SUP] 3 [/SUP], Jim Yee[SUP] 7 [/SUP], Roshni Patel[SUP] 1 [/SUP], Juan Dizon[SUP] 1 [/SUP], Cecille Unson-O'Brien[SUP] 1 [/SUP], Irina Shimeliovich[SUP] 1 [/SUP], Davide F Robbiani[SUP] 8 [/SUP], Zhen Zhao[SUP] 7 [/SUP], Anna Gazumyan[SUP] 1 [/SUP], Robert E Schwartz[SUP] 5 9 [/SUP], Theodora Hatziioannou[SUP] 2 [/SUP], Pamela J Bjorkman[SUP] 4 [/SUP], Saurabh Mehandru[SUP] 10 [/SUP], Paul D Bieniasz[SUP] 11 12 [/SUP], Marina Caskey[SUP] 13 [/SUP], Michel C Nussenzweig[SUP] 14 15 [/SUP]
Affiliations
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[SUP]1,2[/SUP]. 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 titres decrease significantly with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold 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 the onset of coronavirus disease-2019 (COVID-19), 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.
. 2021 Jan 18.
doi: 10.1038/s41586-021-03207-w. Online ahead of print.
Evolution of antibody immunity to SARS-CoV-2
Christian Gaebler[SUP] #[/SUP][SUP] 1 [/SUP], Zijun Wang[SUP] #[/SUP][SUP] 1 [/SUP], Julio C C Lorenzi[SUP] #[/SUP][SUP] 1 [/SUP], Frauke Muecksch[SUP] #[/SUP][SUP] 2 [/SUP], Shlomo Finkin[SUP] #[/SUP][SUP] 1 [/SUP], Minami Tokuyama[SUP] #[/SUP][SUP] 3 [/SUP], Alice Cho[SUP] #[/SUP][SUP] 1 [/SUP], Mila Jankovic[SUP] #[/SUP][SUP] 1 [/SUP], Dennis Schaefer-Babajew[SUP] #[/SUP][SUP] 1 [/SUP], Thiago Y Oliveira[SUP] #[/SUP][SUP] 1 [/SUP], Melissa Cipolla[SUP] #[/SUP][SUP] 1 [/SUP], Charlotte Viant[SUP] 1 [/SUP], Christopher O Barnes[SUP] 4 [/SUP], Yaron Bram[SUP] 5 [/SUP], Ga?lle Breton[SUP] 1 [/SUP], Thomas H?ggl?f[SUP] 1 [/SUP], Pilar Mendoza[SUP] 1 [/SUP], Arlene Hurley[SUP] 6 [/SUP], Martina Turroja[SUP] 1 [/SUP], Kristie Gordon[SUP] 1 [/SUP], Katrina G Millard[SUP] 1 [/SUP], Victor Ramos[SUP] 1 [/SUP], Fabian Schmidt[SUP] 2 [/SUP], Yiska Weisblum[SUP] 2 [/SUP], Divya Jha[SUP] 3 [/SUP], Michael Tankelevich[SUP] 3 [/SUP], Gustavo Martinez-Delgado[SUP] 3 [/SUP], Jim Yee[SUP] 7 [/SUP], Roshni Patel[SUP] 1 [/SUP], Juan Dizon[SUP] 1 [/SUP], Cecille Unson-O'Brien[SUP] 1 [/SUP], Irina Shimeliovich[SUP] 1 [/SUP], Davide F Robbiani[SUP] 8 [/SUP], Zhen Zhao[SUP] 7 [/SUP], Anna Gazumyan[SUP] 1 [/SUP], Robert E Schwartz[SUP] 5 9 [/SUP], Theodora Hatziioannou[SUP] 2 [/SUP], Pamela J Bjorkman[SUP] 4 [/SUP], Saurabh Mehandru[SUP] 10 [/SUP], Paul D Bieniasz[SUP] 11 12 [/SUP], Marina Caskey[SUP] 13 [/SUP], Michel C Nussenzweig[SUP] 14 15 [/SUP]
Affiliations
- PMID: 33461210
- DOI: 10.1038/s41586-021-03207-w
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[SUP]1,2[/SUP]. 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 titres decrease significantly with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold 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 the onset of coronavirus disease-2019 (COVID-19), 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.