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

Abstract

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, from infection or vaccination, can potently boost spike antibody responses. Less is known about the impact of repeated exposures on Tcell responses. Here, we compare the prevalence and frequency of peripheral SARS-CoV-2-specific Tcell 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 Tcell responders but have less impact on SARS-CoV-2 spike-specific Tcell 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 Tcells displaying a greater polyfunctional potential following hybrid immunity compared with vaccination only. Characterizing adaptive immunity from an evolving viral and immunological landscape may inform vaccine strategies to elicit optimal immunity as the pandemic progress.