LAUSR

The diversity of vaccination modalities and infection history are both variables that have an impact on the immune memory of individuals vaccinated against SARS-CoV-2. To gain more accurate knowledge of how these parameters imprint on immune memory, we conducted a long-term follow-up of SARS-CoV-2 spike protein–specific immune memory in unvaccinated and vaccinated COVID-19 convalescent individuals as well as in infection-naïve vaccinated individuals. Here, we report that individuals from the convalescent vaccinated (hybrid immunity) group have the highest concentrations of spike protein–specific antibodies at 6 months after vaccination. As compared with infection-naïve vaccinated individuals, they also display increased frequencies of an atypical mucosa-targeted memory B cell subset. These individuals also exhibited enhanced TH1 polarization of their SARS-CoV-2 spike protein–specific follicular T helper cell pool. Together, our data suggest that prior SARS-CoV-2 infection increases the titers of SARS-CoV-2 spike protein–specific antibody responses elicited by subsequent vaccination and induces modifications in the composition of the spike protein–specific memory B cell pool that are compatible with enhanced functional protection at mucosal sites. Description Prior SARS-CoV-2 infection increases titers of antibodies elicited by subsequent vaccination and modifies the composition of the memory B cell pool. Highlighting hybrid immunity Most of the population has some immunity to SARS-CoV-2 as a result of prior infection, vaccination, or both. Hybrid immunity to SARS-CoV-2, where an individual has immune memory conferred by both infection and vaccination, is thought to provide superior protection against the virus, though this merits experimental investigation. To that end, Barateau and colleagues conducted a longitudinal analysis comparing individuals who had SARS-CoV-2-specific immunity elicited by infection, vaccination, or both. The authors found that those with hybrid immunity (infection followed by vaccination) had the most robust spike protein–specific antibody response of those analyzed. Individuals with hybrid immunity also presented a distinct CD4+ T and B memory cell landscape. Together, the results of this highlight the superiority of hybrid immunity and suggest that those with prior SARS-CoV-2 infection should still be included in vaccination campaigns. —CM