Impact of SARS-CoV-2 exposure history on the T cell and IgG response

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, from infection or vacci-nation, can potently boost spike antibody responses. Less is known about the impact of repeated exposures on T cell responses. Here, we compare the prevalence and frequency of peripheral SARS-CoV-2-specific T cell and immunoglobulin G (IgG) responses in 190 individuals with complex SARS-CoV-2 exposure histories. As expected, an increasing number of SARS-CoV-2 spike exposures significantly enhances the magnitude of IgG responses, while repeated exposures improve the number of T cell responders but have less impact on SARS-CoV-2 spike-specific T cell frequencies in the circulation. Moreover, we find that the number and nature of exposures (rather than the order of infection and vaccination) shape the spike immune response, with spike-specific CD4 T cells displaying a greater polyfunctional potential following hybrid immu-nity compared with vaccination only. Characterizing adaptive immunity from an evolving viral and immuno-logical landscape may inform vaccine strategies to elicit optimal immunity as the pandemic progress.