Prior SARS‐CoV‐2 Infection Balances Immune Responses Triggered by Four EMA‐approved COVID‐19 Vaccines: an Observational Study

Dear Editor, We have studied humoral and cellular responses in a Spanish cohort of 433 volunteers immunized with four COVID-19 vaccines (Ad26.CoV2.S, BNT162b2, ChAdOx1 and mRNA-1273) approved by the European Medicines Agency (EMA), classified as naïve or recovered according to whether they were previously infected by SARS-CoV-2. Both humoral and cellular responses were higher in those naïve individuals immunized with mRNA-type vaccines (mRNA-1273 and BNT162b2) compared to those inoculated with viral-vector vaccines (ChAdOx1 and Ad26.CoV2.S). These differential responses over time were significantly attenuated in COVID-19-recovered subjects, as in these conditionswedid not find any differences between the four vaccination regimens, neither with one nor two doses of ChAdOx1 or BNT162b2 vaccines in these individuals. We have recently reported that previous medical history of COVID-19 differentially determines the functional B and T cell-mediated responses to BNT162b2 vaccination over time.1 Herein, we have extended that study in a cohort of volunteers vaccinated with four regimens used in Spain. The volunteers were classified as either naïve or recovered according to whether they had been previously infected by the SARS-CoV-2 (Figure 1 and Supporting information Tables S1 and S2). Both BNT162b2 and mRNA-1273 induced higher levels of anti-Spike RBD IgG antibodies than viral-vector vaccines ChAdOx1 and Ad26.CoV2.S, remaining higher at least until 150 days after vaccination (Figure 2A). In addition, mRNA-based vaccines induced higher titers of neutralizing antibodies than viral-vector vaccines, keeping for around 90–150 days (Figure 2B) after which, such differences were not observed. Additionally, mRNA-based vaccines reached higher levels of anti-Spike RBD IgA antibodies than viral-vector vaccines only in the first 3 months post-vaccination (<90 days) perceiving low levels 90–210 days post-vaccination and without differences