BCG revaccination qualitatively and quantitatively enhances SARS-CoV-2 spike-specific neutralizing antibody and T cell responses induced by the COVISHIELDTM vaccine in SARS-CoV-2 seronegative young Indian adults

Abstract

This study tested if prior BCG revaccination can further boost immune responses subsequently induced by an otherwise efficacious Oxford/AstraZeneca ChAdOx1nCoV-19 vaccine, referred to as COVISHIELDTM in India. We compared COVISHIELDTM induced longitudinal immune responses in 21 BCG re-vaccinees (BCG-RV) and 13 BCG-non-revaccinees (BCG-NRV), all of whom were BCG vaccinated at birth and latent tuberculosis negative, after COVISHIELDTM prime and boost with baseline samples that were collected pre-pandemic and pre-BCG revaccination. Compared to BCG-NRV, BCG-RV displayed significantly higher magnitude of spike-specific Ab and T cell responses, including a greater proportion of high responders; better quality polyfunctional CD4 and CD8 T cells that persisted and a more robust Ab and T cell response to the Delta mutant of SARS-CoV-2 highlighting greater breadth. Mechanistically, BCG adjuvant effects on COVISHIELDTM induced adaptive responses was associated with more robust innate responses to pathogen-associated-molecular-patterns through TNF-α and IL-1β secretion. This study highlights the potential of using a cheap and globally available vaccine as an adjuvant to enhance heterologous adaptive immune responses induced by COVIDSHIELDTM and other emerging vaccines.

Fiction and Facts about BCG Imparting Trained Immunity against COVID-19

“…The Netherlands and Germany also showed a significant increase in their confirmed cases per million inhabitants [ 102 ]. The BCG vaccine has been shown to induce heterologous lymphocyte responses against non-specific antigens by eliciting higher production of memory CD4 T-cells and CD8 T-cells to generate an effective immune response against SARS-CoV-2 [ 103 , 104 , 105 ]. Recently, it was shown that immunization with wild-type or recombinant BCG (expressing viral antigens) resulted in an enhancement of a non-specific immune response, with increased secretion of pro-inflammatory cytokines and T-cell activation upon antigenic stimulation [ 106 ].…”

Differences in anti-viral immune responses in individuals of Indian and European origin: relevance for the COVID-19 pandemic

“…Indian participants are healthy healthcare workers of St. John's Medical College Hospital, Bangalore, India, invited to participate between October 2019 and June 2021 (20). All included Indian participants received the BCG vaccination at birth.…”