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

This study tested if prior BCG revaccination can further boost immune responses subsequently induced by a widely distributed and otherwise efficacious Oxford/AstraZeneca ChAdOx1nCoV-19 vaccine, referred to as COVISHIELD(™), in India. We compared COVISHIELD(™) 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 COVISHIELD(™) 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 COVISHIELD(™) induced adaptive responses was associated with more robust innate responses to pathogen-associated-molecular-patterns through TNF-α and IL-1β secretion. This study provides first in-depth analysis of immune responses induced by COVISHIELD(™) in India and highlights the potential of using a cheap and globally available vaccine, BCG, as an adjuvant to enhance heterologous adaptive immune responses induced by COVIDSHIELD(™) and other emerging vaccines.