1. Introduction
The constant mutations in SARS-CoV2 the Spike protein have given rise to number of VOCs all of which had potential to evade the memory immune cells arising due to vaccination1. In particularly the second wave caused by Delta variant wreaked havoc all throughout the world. In India also the wave caused by Delta variant was most destructive in terms of loss of life2. In India 10 vaccines have been approved ChAdOx-1 S (AstraZeneca/Serum Institute of India), BBV152 (Bharat Biotech), Ad26.COV2. S (Johnson and Johnson), BECOV2D (Biologicals E Ltd.), Gam-COVID-Vac (Gamaleya Research Institute of Epidemiology and Microbiology.), mRNA-1273(Moderna), NVX-CoV2373 (Serum Institute of India), ZyCoV-D (Zydus Cadilla), Sputnik light (Gamaleya Research Institute of Epidemiology and Microbiology), Lyophilized mRNA Vaccine for Injection (COVID-19) [HGCO-19] (Gennova Biopharmaceuticals), BBV154 - Adenovirus vectored, intranasal vaccine (iNCOVACC) (Bharat Biotech).
The exact extent of protection by vaccines given against different variants is varied according to different reports. BBV152 (Covaxin) is an inactivated vaccine developed in India, which have been approved by the WHO and have been widely used in several countries. It is still a matter of scientific debate that whether inactivated vaccinees are still working against variants of concern. Most of the studies looked into neutralization antibodies to understand the protection conferred by these vaccines but the role of CD4+T cells is still not clear. An earlier study from India revealed that the BBV152 vaccine displayed low neutralization reductions against variants of concerns but elicited a robust T cell response3. But even after vaccinations a large number of people were infected with different variants of concerns in successive Covid-19 waves indicating that complexity of immunological protection imparted by vaccination is still illusive in case of Covid-19 vaccines. CD4+ T cells are major players that impart protection against viral infections and within the CD4+ T cell subset the role CD4+T follicular cells (Tfh) have been instrumental in helping B cells to produce different isotypes of immunoglobulins and for their affinity maturation4. But their role in SARS-CoV2 vaccination induced protection and how their phenotype is affected after breakthrough infection is still not clear. So, to understand Tfh response in this study we investigated the phenotype and response of Tfh cells in healthy volunteers who were vaccinated with BBV154 (inactivated whole virus vaccine) and had breakthrough infection along with volunteers who were also vaccinated but did not contract the virus during the second wave in India which was mainly driven by Delta variant of SARS-CoV2.