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

During the COVID-19 pandemic, large differences in susceptibility and mortality due to SARS-CoV-2 infection have been reported between populations in Europe and South Asia. While both host and environmental factors (including BCG vaccination) have been proposed to explain this, the potential biological substrate of these differences is unknown. We purified peripheral blood mononuclear cells from individuals living in India and the Netherlands at baseline and 10-12 weeks after BCG vaccination. We compared chromatin accessibility between the two populations at baseline, as well as gene transcription profiles and cytokine production capacities upon viral stimulation with influenza and SARS-CoV-2. The chromatin accessibility of genes important for adaptive immunity was higher in Indians compared to Europeans, while the latter had more accessible chromatin regions in genes of the innate immune system. At the transcriptional level, we observed that Indian volunteers displayed a more tolerant immune response to viral stimulation, in contrast to a more exaggerated response in Europeans. BCG vaccination strengthened the tolerance program in Indians, but not in Europeans. These differences may partly explain the different impact of COVID-19 on the two populations.

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 (preprint)

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.