ABSTRACT
Medical history of COVID-19 was an exclusion criterion in the clinical trial that led to the vaccination regimen of two-doses for the BNT162b2 SARS-CoV-2 mRNA vaccine. Herein, we have analyzed a wide panel of immune responses triggered by this immunization in a cohort of naïve and COVID-19-recovered individuals. Plasma levels of S-specific immunoglobulins peaked after one vaccine shot in COVID-19-recovered individuals, while a second dose was needed in naïve subjects to achieve similar levels. However, naïve individuals did not reach as much neutralizing titers as COVID-19-recovered participants did after a complete vaccination regimen. At that point, after T cell stimulation with S-protein antigens from SARS-CoV-2, naïve individuals exhibited higher cytokine production levels, CD4+ T cells activation and proliferation than COVID-19-recovered individuals. Moreover, patent inverse correlations were observed between humoral and cellular immune variables, discriminating naïve from COVID-19-recovered subjects. Our data indicate that a previous history of COVID-19 determines the functional T and B cell-mediated responses to BNT162b2 vaccination and, consequently, individual’s history should be considered prior to the vaccination regime.Funding Information: CdF, JGP and JA are supported by Instituto de Salud Carlos III (ISCII). Research in ELC’s lab is supported by Fundación Familia Alonso, Santander Bank, Real Seguros, Fundación Mutua Madrileña, Fundación Uria, Fundación Caixa and Ayuntamiento de Madrid. Declaration of Interests: The authors declare that no conflict of interest exists.Ethics Approval Statement: Informed consent was obtained from all volunteers in accordance with the ethical standards and following the ethical guidelines of the 1975 Declaration of Helsinki. All healthy health personnel data were anonymized before study inclusion