Abstract
SARS-CoV-2 infection rapidly elicits anti-Spike antibodies whose quantity in plasma gradually declines upon resolution of symptoms. This decline is part of the evolution of an immune response leading to B cell differentiation into short-lived antibody-secreting cells or resting memory B cells. At the same time, the ongoing class switch and antibody maturation processes occurring in germinal centers lead to the selection of B cell clones secreting antibodies with higher affinity for their cognate antigen, thereby improving their functional activity. To determine whether the decline in SARS-CoV-2 antibodies is paralleled with an increase in avidity of the anti-viral antibodies produced, we developed a simple assay to measure the avidity of anti-receptor binding domain (RBD) IgG elicited by SARS-CoV-2 infection. We longitudinally followed a cohort of 29 convalescent donors with blood samples collected between 6- and 32-weeks post-symptoms onset. We observed that, while the level of antibodies declines over time, the anti-RBD avidity progressively increases and correlates with the B cell class switch. Additionally, we observed that anti-RBD avidity increased similarly after SARS-CoV-2 mRNA vaccination and after SARS-CoV-2 infection. Our results suggest that anti-RBD IgG avidity determination could be a surrogate assay for antibody affinity maturation and, thus, suitable for studying humoral responses elicited by natural infection and/or vaccination.
Highlights
Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), leads to the rapid induction of antibodies (Abs) against this virus
We and other researchers have observed that the level of overall antiS and anti-receptor-binding domain (RBD) Abs gradually decline, starting a few weeks following post symptoms onset (PSO) or a few weeks after vaccination [8–15]
This is due to B cell maturation that occurs in the germinal center (GC) leading to a maturation of Abs and enhancing their affinity for their cognate antigen [21]
Summary
Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), leads to the rapid induction of antibodies (Abs) against this virus. Antibody-mediated antiviral activity in plasma is a very complex process and depends on several factors, including the overall levels of antibodies, their respective affinity and avidity for their cognate antigen, and the functional interplay among them [20]. It is well established that after infection or vaccination, antibody avidity increases over time This is due to B cell maturation that occurs in the germinal center (GC) leading to a maturation of Abs and enhancing their affinity (binding strength) for their cognate antigen [21]. While studying the maturation of B cells and associated Abs requires complex technical methods, we developed a simple and robust assay to measure the avidity (overall binding strength) of a polyclonal population of anti-RBD IgG. We used the same assay to measure the increase in avidity of antibodies elicited after one dose of an mRNA vaccine over a period of 12 weeks
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