Polyfunctional CD4 T-cells correlating with neutralising antibody is a hallmark of COVISHIELD^TM and COVAXIN^® induced immunity in COVID-19 exposed Indians.

"Competing interests The authors declare no competing interests."

"We thank the volunteers for participating in this study and acknowledge the contributions of clinical research workers at St John’s Research Institute. With deep regret we would like to inform that SB passed away on the 6th of December 2022 and was not able to review any previous versions of the manuscript prior to submission. We acknowledge contribution of SB (CMC Vellore) in generating the binding and neutralizing antibody data on the samples collected at baseline and two weeks post vaccination. We thank the SJRI FACS facility for help with flow cytometry. The project was fully supported by CSR funding from Hindustan Unilever Limited (HUL) and Unilever India Pvt. Ltd. (UIPL) and facilitated by the Office of the Principal Scientific Advisor (Government of India) and the Department of Atomic Energy (Government of India) under Project No. RTI 4006 to NCBS; the facilities provided by the Bangalore Life Science (BLiSc) and the Research Development Office, are gratefully acknowledged. We acknowledge Dr. Vibhav Sanzgiri and Dr. Janhavi Raut (HUL/UIPL), Dr. Sapna Poti (PSA Office) and Dilip Chenoy (former Secretary General FICCI and DC Skills) for their encouragement. Additional support: S.R. & C.P. were supported by DBT-INDIGO (BT/IN/EU-INF/17/GK/2019–20), V.A. by MRC-GCRF (MR/T039078/1) and NCK & AA by DBT-BIRAC (BT/COVID0073/02/20) grants awarded to A.V. and S.M. by a J.C. Bose Fellowship from the Department of Science and Technology and a Margdarshi Fellowship from the DBT India Alliance (IA/M/15/1/502018)."

"This study was performed in healthy adults aged 18–44 years at St. John’s Research Institute. The trial was approved by the Institutional Ethics Committee (SJRI-298/2021) and registered at the Clinical Trial Registry of India (CTRI) website (CTRI/2021/09/036258). All participants provided written informed consent prior to enrolment. Written informed consent was obtained from all individuals according to the Declaration of Helsinki. SARS-CoV-2 vaccine-naïve participants were screened for serostatus using a combination of anti-spike and/or anti-nucleocapsid antibodies, either qualitative or quantitative, manufactured by either Roche Diagnostics, Abbott Laboratories or Liaison DiaSorin. Recruitment was done using a combination of unbiased as well serostatus-confirmed inclusion. Baseline samples were re-tested and classified for their serostatus using DiaSorin TrimericS and MSD platforms at Christian Medical College, Vellore (see below). Participants with a history of medical illness or prior severe COVID-19 that required ventilation or administration of biologics such as convalescent plasma or monoclonal antibodies were excluded. Vaccine-naïve participants were administered two doses of either COVAXIN® at 4-week interval or COVISHIELDTM at 12-week interval as per the prevailing government norms. Allocation of participants to vaccine arms was non-randomized and per participant-choice. Participants in the COVAXIN® arm were sampled at Day 0 (prior to first dose of vaccine) and Day 42 (2 weeks post-vaccination). Participants in the COVISHIELDTM arm were sampled at Day 0 (prior to the vaccine dose) and Day 98 (2 weeks post-vaccination). Participants were followed bi-monthly for symptoms of COVID-like illness. A consort flow chart showing the details of the recruitment and study protocol has been provided in Supplementary Fig. . The median age of the study population was 28 years (range, 18–44 years), and 65% were male and 35% were female subjects. The details of the study participants were included in Supplementary File ."