The kinetics and longevity of immune responses generated by  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 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.

We will screen individuals for seropositivity against SARS-CoV-2 prior to their vaccination and  then recruit 200 individuals into a prospective cohort study. 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. No specific efforts will be undertaken to modify the vaccine uptake in the cohort other than a general education on the utility of the vaccine and information regarding eligibility as per prevailing government norms. Baseline blood samples will be obtained to separate and store Peripheral Blood Mononuclear Cells (PBMCs) that will be used to assess T-cell and memory B cell profiles. Every two weeks, the cohort will be interviewed telephonically to identify illness compatible with COVID-19, and participants will be asked to contact the study team if they experience any febrile or respiratory illness that necessitates medication or healthcare visit. RT-PCR will be offered to those who meet COVID-19 testing guidelines during an acute illness.

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  laboratory sites Serum, plasma, PBMCs, and saliva will be obtained at study entry (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. For the Covishield group, serum, plasma, PBMCs, and saliva will be obtained at study entry (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 study 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 course of the study. In both studies, skin sampling by scrubs, tapes and swabs will be sampled at baseline and month 6.

Clinical findings and treatment received will be documented throughout the study period.

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 nutritional deficiencies in influencing vaccine outcomes.