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

The kinetics andlongevity of immune responses generated by vaccines in the Indian population are not completely understood.In-depth immunogenicity data and the establishment of platforms to generatesuch data at speed will improve the ability to make public health decisionssuch as the number of vaccine doses required for those with or without priorSARS-CoV-2 infection, need and timing for booster shots, best combination(homologous versus heterologous) of vaccines for boosting, need forincorporating vaccine modifications for circulating strains etc. The studiesproposed here are part of a platform activity to generate immunogenicity dataaddressing the needs of the COVID vaccination program in the country. As afirst step, the primary objective of the studies proposed herein, is tounderstand the differences in magnitude and longevity of humoral and cellularimmune responses generated following vaccination with either Covaxin or Covishield, in those with or withoutevidence of prior SARS-CoV-2 infection based on seropositivity.

 We will screenindividuals for seropositivity against SARS-CoV-2 prior to their vaccinationand  then recruit 200 individuals into aprospective cohort study. The vaccination will be offered with eitherCovishield or Covaxin as per two doses separated by 12 and 4 weeksrespectively, or as per Government of India guidelines at the time of vaccineadministration. No specific efforts will be undertaken to modify the vaccineuptake in the cohort other than a general education on the utility of thevaccine and information regarding eligibility as per prevailing governmentnorms. Baseline blood samples will be obtained to separate and store Peripheral Blood Mononuclear Cells (PBMCs) that will be used to assess T-cell andmemory B cell profiles. Every two weeks, the cohort will be interviewedtelephonically to identify illness compatible with COVID-19, and participantswill be asked to contact the study team if they experience any febrile orrespiratory illness that necessitates medication or healthcare visit. RT-PCRwill be offered to those who meet COVID-19 testing guidelines during an acuteillness.

Vaccinated participantswill be followed up to characterize adaptive immunity (serology, T cell andmemory B cell profiles in blood) as well as innate immunity (antimicrobialpeptides, lipids, skin scrub antimicrobial efficacy tests and microbiomes insaliva and/or skin) across  laboratorysites 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 arebased on current dosing interval of 12 weeks and represent baseline (and firstdose), 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 presecond dose and 2 weeks post second dose will be altered if the policy on thetiming of the second dose is altered during the course of the study. In bothstudies, skin sampling by scrubs, tapes and swabs will be sampled at baselineand month 6.

Clinical findings andtreatment received will be documented throughout the study period.

We will study thekinetics and longevity of humoral and cellular immune responses after vaccinationand whether baseline seropositivity (indication of prior infection) is aneffect modifier. We will also study the role of innate immune markers,microbiomes and nutritional deficiencies in influencing vaccine outcomes.