SARS-CoV-2 infection versus COVID-19 mRNA vaccination-induced Spike-specific memory B cells: frequencies, Ig class and subclass usage, cross-reactivities, and affinity distributions 9044

Abstract Description Owing to differences in exposure route, memory B cells (Bmem) generated following infection of upper airway mucosa with SARS-CoV-2 virus or intramuscular injection of COVID-19 mRNA vaccine may differ in their Ig class/subclass utilization, cross-reactivity profile, and affinity for the Spike (S) antigen. Leveraging ImmunoSpot®, we compared S-specific Bmem in convalescent subjects collected early in the pandemic with naïve individuals that received two COVID-19 mRNA vaccinations encoding the Wuhan-Hu-1 (WH) S antigen. Both convalescent and mRNA vaccinated subjects possessed elevated frequencies of S-specific antibody-secreting cells (ASCs) following polyclonal stimulation of PBMC. However, only convalescent donors possessed Bmem-derived ASC reactivity against WH nucleocapsid protein. S-specific ASCs in convalescent and mRNA vaccinated donors were predominantly IgG1+, but IgG3+ ASC were also detectable. Notably, S-specific IgA+ ASC were detected in nearly all convalescent donors, whereas vaccinated donors exhibited considerably lower, if detectable, frequencies. In contrast, S-specific IgG4+ ASC were only detected in mRNA vaccinated subjects. Nevertheless, both convalescent and mRNA vaccinated subjects possessed elevated frequencies of Bmem with cross-reactivity for the receptor binding domain (RBD) of future variants. Lastly, titration of RBD probes in inverted ImmunoSpot® assays suggested Bmem in convalescent and mRNA vaccinated subjects underwent similar affinity maturation. Funding Sources This work was fully funded from the research budget of CTL Topic Categories Vaccines and Immunotherapy (VAC)