Interim results from comparison of immune responses elicited by an inactivated and a vectored SARS-CoV-2 vaccine in seronegative and seropositive participants in India
Authors: Asokan Mangaiarkarasi , Joan Roshni Florina , Babji Sudhir , Dayma Girish , Nitheesh Prajitha , Subrahmanyam Vinutha , Pandey Archana , Malagi Girish , Arya Pooja , Mahajan Vibhuti , Bhavikatti Jayateerth , Pawar Ketakee , Thorat Aishwarya , Shah Priyanki , Goud Ramakrishna B , Roy Bishnudeo , Rajukutty Shon , Immanuel Sushil , Agarwal Dhiraj , Saha Sankhanil , Shivaraj Akshatha , Panikulam Patricia , Shome Rajeshwari , Gulzar Shah-E-Jahan , Sharma Anusmrithi U , Naik Ajinkya , Talashi Shruti , Belekar Madhuri , Yadav Ritu , Khude Poornima , Mamatha V , Sudarshan S , Deshmukh Urmila , Bhise Chinmayee , Joshi Manjiri , Inbaraj Leeberk Raja , Chandrasingh Sindhulina , Ghose Aurnab , Jamora Colin , Karumbati Anandi S , Sundaramurthy Varadharajan , Johnson Avita , Ramesh Naveen , Chetan Nirutha , Parthiban Chaitra , Ahmed Asma , Rakshit Srabanti , Adiga Vasista , D’souza George , Rale Vinay , George Carolin Elizabeth , John Jacob , Kawade Anand , Chaturvedi Akanksha , Raghunathan Anu , Dias Mary , Bhosale Anand , Raghu Padinjat , Shashidhara LS , Vyakarnam Annapurna , Bal Vineeta , Kang Gagandeep , Mayor Satyajit 
Published: January 2023

AbstractBackgroundThere are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the 18 to 45-year age-group began in April 2021 when seropositivity rates in the general population were rising due to the Delta wave in April-May 2021.MethodsBetween 30 June 2021 and 28 January 2022, we enrolled 691 participants in the 18-45 age group across 4 clinical sites in India. In this non-randomized and laboratory blinded study, participants received either two doses of Covaxin®4 weeks apart or two doses of Covishield™ 12 weeks apart per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titer (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination.FindingsWhen compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield™ elicited higher antibody responses than Covaxin®as measured by seroconversion rate (98.3% vs 74.4%, p<0.0001 in seronegative individuals; 91.7% vs 66.9%, p<0.0001 in seropositive individuals) as well as by anti-spike antibody levels against the ancestral strain (GMT 1272.1 vs 75.4 BAU/ml, p<0.0001 in seronegative individuals; 2089.07 vs 585.7 BAU/ml, p<0.0001 in seropositive individuals). Not all sites recruited at the same time, therefore site-specific immunogenicity was impacted by the timing of vaccination relative to the Delta and Omicron waves. Surrogate neutralizing antibody responses against variants-of-concern were higher in Covishield™ recipients than in Covaxin®recipients and in seropositive than in seronegative individuals after both vaccination and asymptomatic Omicron infection. T cell responses are reported from only one of the four site cohorts where the vaccination schedule preceded the Omicron wave. In seronegative individuals, Covishield™ elicited both CD4+ and CD8+ spike-specific cytokine-producing T cells whereas Covaxin®elicited mainly CD4+ spike-specific T cells. Neither vaccine showed significant post-vaccination expansion of spike-specific T cells in seropositive individuals.InterpretationCovishield™ elicited immune responses of higher magnitude and breadth than Covaxin®in both seronegative individuals and seropositive individuals, across cohorts representing the pre-vaccination immune history of the majority of the vaccinated Indian population.