ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
This article is part of the Research TopicEnigma Unmasked: Deciphering the Humoral Immune Response in Long COVIDView all 3 articles
Long-Term Humoral and Cellular Immune Responses Following Covaxin Vaccination: A Two-Year Prospective Longitudinal Study
Provisionally accepted
Sunil Kumar Raghav1*
Archana Tripathy1Sreeparna Podder1Swatishree Sradhanjali1Mamuni Swain1
Debdutta Bhattacharya2
Debaprasad Parai2Sanghamitra Pati2- 1Institute of Life Sciences (ILS), Bhubaneswar, India
- 2ICMR-Regional Medical Research Centre, Bhubaneswar, India
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Background: Globally, multiple SARS-CoV-2 vaccines received emergency authorization, primarily based on adenoviral vector, mRNA, or inactivated virus platforms. Among them, Covaxin, an inactivated vaccine, was widely used in India and several Southeast Asian countries. Due to their emergency rollout in 2021, the long-term immunogenicity data to assess the impact of these vaccinations has been limited. This study investigated the prolonged immune responses induced by Covaxin, an inactivated virus-based COVID-19 vaccine in 250 individuals monitored for two years. Methods: This longitudinal study (Jan 2021-Jan 2023) tracked 250 participants, collecting blood at seven time points. We measured SARS-CoV-2 spike RBD IgG and neutralizing antibodies using ECLIA and surrogate virus neutralization tests, respectively. We also assessed cellular immunity in a subset of Covaxin recipients through flow cytometry of spike protein-stimulated lymphocytes. Result: Anti-RBD IgG levels declined rapidly post-vaccination, a significant rise was observed following Omicron infection, with sustained high antibody titres and high virus neutralization capacity. Covaxin recipients demonstrated high CD4+ T-cell activity during the Omicron wave, correlating with mild or asymptomatic infections. These findings suggests that Omicron exposure may have served as a natural booster and holds potential for next-generation vaccine development for COVID. Enhanced T-cell responses, particularly after the third dose further underscored the vaccine’s ability to maintain cellular immunity. Compared with Covishield, Covaxin elicited milder immune responses, possibly contributing to its favourable safety profile. Conclusions: Overall, this study provides one of its first longitudinal analyses of the humoral and T-cell responses to Covaxin, a vaccine widely administered in India and neighbouring Southeast Asian countries.
Keywords: AIM (activationinduced markers), Covaxin, COVID-19, Longitudinal cohort, Neutralizing antibody (NAb), Receptor BindingDomain (RBD), SARS-CoV-2, spike (S)
Received: 26 Nov 2025; Accepted: 10 Feb 2026.
Copyright: © 2026 Raghav, Tripathy, Podder, Sradhanjali, Swain, Bhattacharya, Parai and Pati. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sunil Kumar Raghav
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