Inactivated virus vaccine BBV152/Covaxin elicits robust cellular immune memory to SARS-CoV-2 and variants of concern

Abstract

The characteristics of immune memory established in response to inactivated SARS-CoV-2 vaccines remains unclear. We determined the magnitude, quality and persistence of cellular and humoral memory responses up to 6 months after vaccination with BBV152/Covaxin. Here, we show that the quantity of vaccine-induced spike- and nucleoprotein-antibodies is comparable to that following natural infection and the antibodies are detectable up to 6 months. The RBD-specific antibodies decline in the range of 3 to 10-fold against the SARS-CoV-2 variants in the order of alpha (B.1.1.7) > delta (B.1.617.2) > beta (B.1.351), with no observed impact of gamma (P.1) and kappa (B.1.617.1) variant. We found that the vaccine induces memory B cells, similar to natural infection, which are impacted by virus variants in the same order as antibodies. The vaccine further induced antigen-specific functionally potent multi-cytokine expressing CD4+ T cells in ∼85% of the subjects, targeting spike and nucleoprotein of SARS-CoV-2. Marginal ∼1.3 fold-reduction was observed in vaccine-induced CD4+ T cells against the beta variant, with no significant impact of the alpha and the delta variants. The antigen-specific CD4+ T cells were populated in the central memory compartment and persisted up to 6 months of vaccination. Importantly the vaccine generated Tfh cells that are endowed with B cell help potential, similar to the Tfh cells induced after natural infection. Altogether, these findings establish that the inactivated virus vaccine BBV152 induces robust immune memory to SARS-CoV-2 and variants of concern, which persist for at least 6 months after vaccination. This study provides insight into the attributes of BBV152-elicited immune memory, and has implication for future vaccine development, guidance for use of inactivated virus vaccine, and booster immunization.

Immunogenicity and reactogenicity of an inactivated SARS-CoV-2 vaccine (BBV152) in children aged 2–18 years: interim data from an open-label, non-randomised, age de-escalation phase 2/3 study

“… 13 , 16 An earlier study in adults vaccinated with BBV152 reported cross-reactive T-cell responses to several SARS-CoV-2 variants (alpha, beta, and delta). 20 …”

“…Vikkurthi and colleagues, also show (in a preprint) that, ex vivo, BBV152-generated T cells (Tfh) assist in B-cell production of antibodies against SARS-CoV-2 variants of concern. 20 …”

Protective efficacy of COVAXIN® against Delta and Omicron variants in hamster model

“…COVAXIN® was found to induce robust immune memory and Th1 skewed response in previous studies. 23,24 The vaccine was also found to elicit a substantial fraction of T follicular cells which in turn can aid in long term humoral immunity. 23 The proportion of the antibody secreting memory B cells in the 3 dose COVAXIN® recipients were found more compared to the 2 dose recipients.…”

“…10,20 Apart from B cell mediated immunity, the SARS-CoV-2 specific central and effector memory cells which can aid in cytotoxic function (CD8+ TEMRA phenotype) has been demonstrated in the COVAXIN® recipients. 23 These properties could have attributed to the rapid reduction of viral load after challenge. Although marked difference was not observed in the histopathological cumulative score of the BA.1.1 infected groups, the mean score of the vaccinated groups were considerably lower compared to our earlier studies on pathogenicity of BA.1.1 in hamster.…”

“…23,24 The vaccine was also found to elicit a substantial fraction of T follicular cells which in turn can aid in long term humoral immunity. 23 The proportion of the antibody secreting memory B cells in the 3 dose COVAXIN® recipients were found more compared to the 2 dose recipients. 10 For COVAXIN®, an effectiveness of 69% has been reported against severe COVID-19 and 50% against symptomatic COVID-19 for Delta variant in humans after 2 dose vaccinations.…”