Lessons from COVID-19 vaccines: high dimensional analyisis of specific T and B cell immune response reveals distinct immunological signatures in 16 combinations of vaccines

The range of vaccines developed against SARS-CoV-2 gave a unique opportunity to study immunization across different platforms. In a single-center cohort with more than 400 volunteers, we analysed the humoral and cellular immune compartments following five COVID-19 vaccines spanning three technologies (adenoviral, mRNA, and inactivated-virus) administered in 16 combinations. Quantification of specific IgG and IgA anti-spike together with the evaluation of the neutralizing activity of the sera, measurement of spike-specific IFNϒ production, and single cell proteomic analysis of spike-binding memory B cells allowed us to determine four clearly distinct immune signatures elicited by the different vaccine combinations. Our data indicate that the immune response is shaped by the type of vaccines applied and by the order in which they are delivered. Our data provide a framework for improving future vaccines strategies against pathogens and cancer.