Impact in the humoral and cellular immune response to SARS-CoV-2 variants after primary vaccination with AZD1222/COVISHIELD protocol in healthy adults.

SARS-CoV-2 emerged rapidly as a pandemic, leading to the urgent development and authorization for the use of several vaccines, with questions relating to immunogenicity in previously infected people or to virus variants. As such, we sought to determine the humoral and cellular immune response of healthy adults to distinct SARS-CoV-2 variants upon AZD1222/COVISHIELD vaccination, using chemiluminescence (CMIA), neutralizing antibody (PRNT) and analysis of activation-induced marker (AIM) by flow cytometry, respectively. We enrolled 75 volunteers, including 26 individuals previously infected with SARS-CoV-2. Our findings demonstrated that AZD1222 vaccine induced increased levels of SARS-CoV-2-specific antibodies after two-dose vaccination scheme, as detected by CMIA (mean = 49 BAU/mL to 743 BAU/mL) and PRNT (GMT = 3, 95 % CI 2-4, to 19, 11-34). After vaccination, all volunteers presented detectable antibodies by CMIA while only 64 % presented positive PRNT. Seroconversion rates were 91 % and 48 % by CMIA and 59 % by PRNT after the first and second dose, respectively. The PRNT to Delta variant demonstrated lower titers as compared to Wuhan-like and a seroconversion of 57 %. Although by CMIA all volunteers were classified as high responders, some volunteers showed no response by PRNT and AIM. In general, previously infected volunteers had higher post-vaccination antibody titers after each dose. CD4 T cell response was generally higher than CD8 T cells for all variants. Overall, we observed that AZD1222 vaccination induced cross-reactivity to SARS-CoV-2 variants, in both cellular and humoral responses. During volunteer follow-up, we observed that the elevated antibody titers are lasting and were incremented by the first booster. In conclusion, our findings showed that AZD1222 vaccine was able to induce a robust immune response upon primary immunization, with cross-reactivity for the Delta VOC.