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.