mRNA COVID-19 vaccine elicits potent adaptive immune response without the acute inflammation of SARS-CoV-2 infection [CV2]

SARS-CoV-2 infection and vaccination elicit potent immune responses. Our study presents a comprehensive multimodal single-cell dataset of peripheral blood of patients with acute COVID-19 and of healthy volunteers before and after receiving the SARS-CoV-2 mRNA vaccine and booster. We compared host immune responses to the virus and vaccine using transcriptional profiling, coupled with B/T cell receptor repertoire reconstruction. COVID-19 patients displayed an enhanced interferon signature and cytotoxic gene upregulation, absent in vaccine recipients. These findings were validated in an independent dataset. Analysis of B and T cell repertoires revealed that, while the majority of clonal lymphocytes in COVID-19 patients were effector cells, clonal expansion was more evident among circulating memory cells in vaccine recipients. Furthermore, while clonal aß T cell responses were observed in both COVID-19 patients and vaccine recipients, dramatic expansion of clonal gdT cells was found only in infected individuals. Our dataset enables comparative analyses of immune responses to infection versus vaccination, including clonal B and T cell responses. Taken together, our comparative analysis shows that vaccination induces a robust adaptive immune response, including a durable clonal B and T cell response, without the severe inflammation associated with infection. Overall design: We profiled crculating immune cells from five adults with acute COVID-19 infection and nine healthy adults, seven of whom received theBNT162b2 vaccine. For three of the vaccine recipients, samples were also collected before and after receiving a booster. Samples were taken at multiple time points, resulting in a total of 42 post-vaccination and 9 post-infection samples