Memory B cells control SARS-CoV-2 variants upon mRNA vaccination of naive and COVID-19 recovered individuals

Abstract

How a previous SARS-CoV-2 infection may amplify and model the memory B cell (MBC) response elicited by mRNA vaccines was addressed by a comparative longitudinal study of two cohorts, naive individuals and disease-recovered patients, up to 2 months after vaccination. The quality of the memory response was assessed by analysis of the VDJ repertoire, affinity and neutralization against variants of concerns (VOC), using unbiased cultures of 2452 MBCs. Upon boost, the MBC pool of recovered patients selectively expanded, further matured and harbored potent neutralizers against VOC. Maturation of the MBC response in naive individuals was much less pronounced. Nevertheless, and as opposed to their weaker neutralizing serum response, half of their RBD-specific MBCs displayed high affinity towards multiple VOC and one-third retained neutralizing potency against B.1.351. Thus, repeated vaccine challenges could reduce these differences by recall of affinity-matured MBCs and allow naive vaccinees to cope efficiently with VOC.

Anti- SARS-CoV-2 Receptor Binding Domain Antibody Evolution after mRNA Vaccination

“…Plasma IgM, IgG, and IgA responses to SARS-CoV-2 receptor binding domain (RBD) were measured by enzyme linked immunosorbent assay (ELISA) 3 . As reported by others 2,[4][5][6] there was a significant increase in IgG reactivity to RBD between prime and boost (p<0.0001, Fig. 1a).…”

“…Notably, neutralization titres elicited by vaccination exceed those of COVID-19 recovered individuals at all comparable time points assayed. Nevertheless, neutralizing potency against variants is significantly lower than against Wuhan Hu-1, with up to 5-10-fold reduced activity against the B.1.351 variant 5,6,13,14,38 . Taken together with the overall decay in neutralizing activity there can be 1-2 orders of magnitude decrease in serum neutralizing activity after or months against variants when compared to the peak of neutralizing activity against Wuhan Hu-1.…”

“…The increase in potency and breadth in the memory compartment that develops after natural infection accounts for the exceptional responses to Wuhan Hu-1 and its variants that convalescent individuals develop when boosted with mRNA vaccines 1,5 . The expanded memory B cell compartment in mRNA vaccinees should also produce high titers of neutralizing antibodies when vaccinees are boosted or when they are re-exposed to the virus 52 .…”

“…(3) baseline: 200sec immersion in buffer. (4) Association: 300sec immersion in solution with WT RBD at 20, 10 or 5 μg/ml (5) dissociation: 600sec immersion in buffer. Curve fitting was performed using a fast 1:1 binding model and the Data analysis software (ForteBio).…”

“…(3) baseline: 200sec immersion in buffer. (4) Association: 300sec immersion in solution with WT RBD at 20, 10 or 5 μg/ml(5)…”