AUTHOR=Esparcia-Pinedo Laura , Martínez-Fleta Pedro , Ropero Noelia , Vera-Tomé Paula , Reyburn Hugh T. , Casasnovas José M. , Rodríguez Frade José M. , Valés-Gómez Mar , Vilches Carlos , Martín-Gayo Enrique , Muñoz-Calleja Cecilia , Sanchez-Madrid Francisco , Alfranca Arantzazu TITLE=CD4+ T Cell Immune Specificity Changes After Vaccination in Healthy And COVID-19 Convalescent Subjects JOURNAL=Frontiers in Immunology VOLUME=Volume 12 - 2021 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.755891 DOI=10.3389/fimmu.2021.755891 ISSN=1664-3224 ABSTRACT=The characterization of immune responses promoted by SARS-CoV-2 vaccination is of utmost relevance for the development of novel vaccines and optimized prevention strategies. We analyzed changes in adaptive immunity in healthy donors (HD) and convalescent individuals (CD), before and after administration of BNT162b2 vaccine. Our results revealed specific changes in CD4+ T cell reactivity profile in vaccinated HD and CD, which showed an increase in S1 and S2 positive individuals, proportionally higher for S2. On the contrary, NCAP reactivity observed in both HD and CD patients was no longer detectable after vaccination. Despite the substantial antibody response in CD, MPro-derived peptides did not elicit CD4+ lymphocyte activation in our assay in either condition. Upon vaccination, HD presented an increment in anti-S and anti-RBD IgG after first dose inoculation, which was further increased after the second injection. Conversely, anti-S and anti-RBD IgG and IgA titers increased in already positive CD after first dose administration, remaining stable upon second dose inoculation. Interestingly, we found a strong significant correlation between S1-induced CD4+ response and anti-S IgA prior to vaccination, which was lost after vaccine administration.