A prospective two-year longitudinal follow-up study depicting humoral and cell-mediated immune responses in Covaxin vaccinated individuals

There are majorly two variants of SARS-CoV-2 vaccine that were employed worldwide on emergency basis to contain the COVID-19 pandemic i.e., RNA based or adenovirus construct based Spike protein expression system which was broadly used and the inactivated virus particle composition. Due to emergency usage starting from the onset of 2021, the immunogenicity data pertaining to long term effects of these vaccines is unexplored. Therefore, in this study we assessed the immunogenicity analysis of Covaxin (BBV152), an inactivated virus-based vaccine for a longitudinal time-span of two years. We investigated the humoral and cell-mediated immune responses in 250 subjects for two years by estimating the RBD specific IgG titres and CD4+/CD8+ T-cell responses. We found that anti-RBD IgG titres that were almost reaching at the basal levels within a year of 2nd dose of vaccination, went significantly high immediately after Omicron infection wave in January 2022. Moreover, the pseudo-virus neutralization by the serum of these subjects showed concordant and drastic increase in virus neutralization activity. At the same time, mild or no symptoms were observed in individuals infected with Omicron variant of SARS-CoV-2. These observations strongly suggested that Omicron variant could have been the best SARS-CoV-2 variant for effective vaccine formulations to generate robust protective immune response along with lesser side effects. Interestingly, the CD4+ and CD8+T-cell activity in Covaxin vaccinees depicted mild to moderate but sustained responses. The spike peptivator pool activated PBMCs of vaccinees depicted an enhancement of CD4+ and CD8+ antigenic responses after 2nd and 3rd dose of vaccine administration. In comparison to Covishield, the antibody and T-cell responses were found to be milder in BBV152 vaccinees. This milder antibody and T-cell response could be the reason behind no or less side effects with BBV152 administration than other RNA based vaccines. Overall, our study is one of the first studies profiling the longitudinal humoral and T-cell responses of inactivated virus-based vaccines like COVAXIN, which was predominantly used in India and neighbouring Southeast Asian countries. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by DBT, BIRAC (BT/CS0053/05/21) and ILS Core Grant ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of Institute of Life Sciences gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors