No abstract

The elicited anti-SARS-CoV-2 immunity is becoming increasingly complex with individuals receiving a different number of vaccine doses paired with or without recovery from breakthrough infections with different variants. Here we analyze the immunity of individuals that initially received two doses of mRNA vaccine and either received a booster vaccination, recovered from a breakthrough infection, or both. Our data suggest that two vaccine doses and delta breakthrough infection or three vaccine doses and optionally omicron or delta infection provide better B cell immunity than the initial two doses of mRNA vaccine with or without alpha breakthrough infection. A particularly potent B cell response against the currently circulating omicron variant (B. 1.1.529) was observed for thrice vaccinated individuals with omicron breakthrough infection; a 46-fold increase in plasma neutralization compared to two vaccine doses (p < 0.0001). The T cell response after two vaccine doses is not significantly influenced by additional antigen exposures. Of note, individuals with hybrid immunity show better correlated adaptive immune responses compared to those only vaccinated. Taken together, our data provide a detailed insight into SARS-CoV-2 immunity following different antigen exposure scenarios.

BackgroundWorldwide vaccination campaigns significantly reduced mortality caused by SARS-CoV-2 infection and diminished the devastating effects of the pandemic. The first approved vaccines are based on novel mRNA technology and elicit potent immune responses offering high levels of protection from severe disease.MethodsHere we longitudinally assessed adaptive immune responses during a 12-month follow-up period after the initial immunization with 2 doses of mRNA vaccines and after the booster dose in blood and saliva.ResultsOur findings demonstrate a rapid waning of the anti-spike IgG titers between months 3 and 6 after the initial vaccination (1.7- and 2.5-fold decrease in plasma and saliva, respectively; P&lt;0.0001). Conversely, the frequency of spike-specific memory B cells increased during this period (2.4-fold increase; P&lt;0.0001) while the frequency of spike-specific CD4+ and CD8+ T cells remained stable for all assessed functions: cytotoxicity, IFNγ, IL-2, and TNFα expression. Booster vaccination significantly improved the antibody response in plasma and saliva, with the most profound changes observed in the neutralization capacity against the currently circulating omicron variant (25.6-fold increase; P&lt;0.0001). The positive effect of booster vaccination was also evident for spike-specific IgG+ memory B cell (2.4-fold increase; P&lt;0.0001) and cytotoxic CD4+ and CD8+ T cell responses (1.7- and 1.9-fold increase respectively; P&lt;0.05).ConclusionsCollectively, our findings offer a detailed insight into the kinetics of adaptive immune response following SARS-CoV-2 vaccination and underline the beneficial effects of a booster vaccination.