Study on Long-term Immunogenicity of COVID-19 vaccines in vaccine-naïve seronegative and seropositive participants

There are currently three approved Coronavirus Disease (COVID) vaccines in India, of which two have been in use widely (Covishield and Covaxin), and a third vaccine (Sputnik V) is becoming available. The kinetics and longevity of immune responses generated by these vaccines in the Indian population are not completely understood. In-depth immunogenicity data and the establishment of platforms to generate such data at speed will improve the ability to make public health decisions such as the number of vaccine doses required for those with or without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, need and timing for booster shots, best combination (homologous versus heterologous) of vaccines for boosting, need for incorporating vaccine modifications for circulating strains etc. The studies proposed here are part of a platform activity to generate immunogenicity data addressing the needs of the COVID vaccination program in the country. As a first step, the primary objective of the studies proposed herein, is to understand the differences in magnitude and longevity of humoral and cellular immune responses generated following vaccination with either Covaxin or Covishield, in those with or without evidence of prior SARS-CoV-2 infection based on seropositivity.   From across two cities and four institutes (Bangalore Baptist Hospital, St. John’s Research Institute Bangalore, Symbiosis University Hospital and Research Centre Pune and KEM Hospital Research Centre Pune), we will screen individuals for seropositivity against SARS-CoV-2 prior to their vaccination. The vaccination will be offered with either Covishield or Covaxin as per two doses separated by 12 and 4 weeks respectively, or as per Government of India guidelines at the time of vaccine administration. If the interval between two doses changes, then the blood timepoint will be changed appropriately. Total 800 participants, 200 at each study site will be recruited. No specific efforts will be undertaken to modify the vaccine uptake in the participating individuals other than a general education on the utility of the vaccine and information regarding eligibility as per prevailing government norms. Baseline blood, skin and saliva samples will be obtained. Every two weeks, the participants will be contacted through home/phone visit to identify illness compatible with COVID-19. The participants having COVID- like illness since their last contact or had history of contact with a confirmed case of SARS-CoV-2 infection, then nasopharyngeal swab and/or saliva will be collected for Reverse Transcription -Polymerase Chain Reaction (RT-PCR) testing for SARS-CoV-2 infection. The participants confirmed with SARS-CoV-2 illness will be managed as per standard of care and national guidelines. The individuals once recover from the breakthrough infection will be requested to provide 27 ml blood and 5 ml saliva sampling for immunological and virological analysis. During the course of the study, vaccinated participants will be followed up to characterize adaptive immunity (serology, T cell and memory B cell profiles in blood) as well as innate immunity (antimicrobial peptides, lipids, skin scrub antimicrobial efficacy tests and microbiomes in saliva and/or skin) across seven laboratory sites namely namely National Centre for Biological Sciences (NCBS), Bangalore, InStem Bangalore, St. John’s Research Institute (SJRI) Bangalore, Christian Medical College (CMC) Vellore, Indian Institute of Science Education and Research (IISER) Pune, National Chemical Laboratory (NCL) Pune. Blood (to obtain Serum, plasma, and Peripheral Blood Mononuclear Cells (PBMCs)) and saliva samples will be collected to at the baseline (Day 0) and at Day 28 (+2 d), Day 42 (+2 d), Day 84 (+7 d), Month 6 (+7 d) and Month 9 (+7 d) following the first dose of Covaxin from the Covaxin groups. For the Covishield groups, blood (to obtain serum, plasma, PBMCs) and saliva samples will be obtained at the baseline (Day 0) and at Day 28 (+2 d), Day 84 (+7 d), Day 98 (+2 d), Month 6 (+7 d) and Month 9 (+7 d) following the first dose. These six time points for the Covishield groups are based on current dosing interval of 12 weeks and represent baseline (and first dose), 4 weeks post first dose, pre second dose, 2 weeks post second dose, month 6 and month 9. The day 84 and day 98 sampling times corresponding to pre second dose and 2 weeks post second dose will be altered if the policy on the timing of the second dose is altered during the study. In both groups (Covishield and Covaxin), skin sampling by scrubs (only at Baptist Bangalore), tapes and swabs (at all sites) will be sampled at baseline and month 6. We will study the kinetics and longevity of humoral and cellular immune responses after vaccination and whether baseline seropositivity (indication of prior infection) is an effect modifier. We will also study the role of innate immune markers, microbiomes, and vitamin/mineral deficiencies in influencing immune response to the vaccines.