Longitudinal cellular and humoral immune responses following COVID-19 BNT162b2-mRNA-based booster vaccination of craft and manual workers in Qatar

Background: In March 2020, the rapid spread of SARS-CoV-2 prompted global vaccination campaigns to mitigate COVID-19 disease severity and mortality. The 2-dose BNT162b2-mRNA vaccine effectively reduced infection and mortality rates, however, waning vaccine effectiveness necessitated the introduction of a third vaccine dose or booster. Aim: To assess the magnitude and longevity of booster-induced immunity, we conducted a longitudinal study of SARS-CoV-2 specific cellular and humoral immune responses among Qatar’s vulnerable craft and manual worker community. We also investigated the impact of prior naturally acquired immunity on booster vaccination efficacy. Methods: Seventy healthy participants were enrolled in the study, of whom half had prior SARS-CoV-2 infection. Blood samples were collected before and after booster vaccination to evaluate immune responses through SARS-CoV-2 specific ELISpots, IgG ELISA, neutralization assays, and flow cytometric immunophenotyping. Results: T cell analysis revealed increased Th1 cytokine responses, marked by enhanced IFN-γ release, in recently infected participants, which was further enhanced by booster vaccination for up to 6-months. Furthermore, booster vaccination stimulated cytotoxic responses in infection-naïve participants, characterized by granzyme B production. Both natural SARS-CoV-2 infection and booster vaccination induced robust and durable SARS-CoV-2 specific humoral immune responses, with high neutralizing antibody levels. Prior natural infection was also linked to an increased number of class-switched B cells prior to booster vaccination. Conclusions: These findings underscore the importance of booster vaccination in enhancing anti-viral immunity across both infection-naïve and previously infected individuals, enhancing distinct arms of the anti-viral immune response and prolonging naturally acquired immunity.