Vaccination boosts protective responses and counters SARS-CoV-2-induced pathogenic memory B cells.

Vaccination boosts protective responses and counters SARS-CoV-2-induced pathogenic memory B cells.

Pankaj Kumar Mishra, Natalie Bruiners, Rahul Ukey, Pratik Datta, Alberta Onyuka, Deborah Handler, Sabiha Hussain, William Honnen, Sukhwinder Singh, Valentina Guerrini, Yue Yin, Hannah Dewald, Alok Choudhary, Daniel B Horton, Emily S Barrett, Jason Roy, Stanley H Weiss, Patricia Fitzgerald-Bocarsly, Martin J Blaser, Jeffrey L Carson, Reynold A Panettieri, Alfred Lardizabal, Theresa Li-Yun Chang, Abraham Pinter, Maria Laura Gennaro

Given the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the recent implementation of SARS-CoV-2 vaccination, we have much to learn about the duration of immune protection and the interface between the immune responses to infection and to vaccination. To address these questions, we monitored immune responses to SARS-CoV-2 infection in convalescent individuals over seven months and following mRNA vaccination. Spike Receptor-Binding-Domain (RBD)-specific circulating antibodies and plasma neutralizing activity generally decreased over time, whereas RBD-specific memory B cells persisted. Additionally, using antibody depletion techniques, we showed that the neutralizing activity of plasma specifically resides in the anti-RBD antibodies. More vigorous antibody and B cell responses to vaccination were observed in previously infected subjects relative to uninfected comparators, presumably due to immune priming by infection. SARS-CoV-2 infection also led to increased numbers of double negative B memory cells, which are described as a dysfunctional B cell subset. This effect was reversed by SARS-CoV-2 vaccination, providing a potential mechanistic explanation for the vaccination-induced reduction in symptoms in patients with Long-COVID"."

2021

10.1101/2021.04.11.21255153

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