# Long-term humoral and cellular immune responses following Covaxin vaccination: a 2-year prospective longitudinal study

## TL;DR

This study tracks immune responses to Covaxin over two years, showing that Omicron infections may act as natural boosters and that T-cell immunity remains strong.

## Contribution

The study provides the first detailed 2-year longitudinal analysis of Covaxin's humoral and cellular immune responses.

## Key findings

- Anti-RBD IgG levels declined rapidly but increased significantly after Omicron infection.
- Covaxin recipients showed high CD4+ T-cell activity during the Omicron wave, linked to mild infections.
- Third doses enhanced T-cell responses, highlighting Covaxin's role in maintaining cellular immunity.

## Abstract

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 have been limited. This study investigated the prolonged immune responses induced by Covaxin, an inactivated virus-based COVID-19 vaccine, in 250 individuals monitored for 2 years.

This longitudinal study (January 2021–January 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.

Anti-RBD IgG levels declined rapidly post-vaccination. A significant rise was observed following Omicron infection, with sustained high antibody titers 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 suggest that Omicron exposure may have served as a natural booster and hold 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 favorable safety profile.

Overall, this study provides one of the first longitudinal analyses of the humoral and T-cell responses to Covaxin, a vaccine widely administered in India and neighboring Southeast Asian countries.