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Evidence for the heterologous benefits of prior BCG vaccination on COVISHIELD™ vaccine-induced immune responses in SARS-CoV-2 seronegative young Indian adults

Rakshit, S and Adiga, V and Ahmed, A and Parthiban, C and Chetan Kumar, N and Dwarkanath, P and Shivalingaiah, S and Rao, S and Dâ��Souza, G and Dias, M and Maguire, TJA and Doores, KJ and Zoodsma, M and Geckin, B and Dasgupta, P and Babji, S and van Meijgaarden, KE and Joosten, SA and Ottenhoff, THM and Li, Y and Netea, MG and Stuart, KD and De Rosa, SC and McElrath, MJ and Vyakarnam, A (2022) Evidence for the heterologous benefits of prior BCG vaccination on COVISHIELD™ vaccine-induced immune responses in SARS-CoV-2 seronegative young Indian adults. In: Frontiers in Immunology, 13 .

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Official URL: https://doi.org/10.3389/fimmu.2022.985938


This proof-of-concept study tested if prior BCG revaccination can qualitatively and quantitively enhance antibody and T-cell responses induced by Oxford/AstraZeneca ChAdOx1nCoV-19 or COVISHIELD™, an efficacious and the most widely distributed vaccine 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; latent tuberculosis negative and SARS-CoV-2 seronegative prior to COVISHIELD™ vaccination. Compared to BCG-NRV, BCG-RV displayed significantly higher and persistent spike-specific neutralizing (n) Ab titers and polyfunctional CD4+ and CD8+ T-cells for eight months post COVISHIELD™ booster, including distinct CD4+IFN-γ+ and CD4+IFN-γ- effector memory (EM) subsets co-expressing IL-2, TNF-α and activation induced markers (AIM) CD154/CD137 as well as CD8+IFN-γ+ EM,TEMRA (T cell EM expressing RA) subset combinations co-expressing TNF-α and AIM CD137/CD69. Additionally, elevated nAb and T-cell responses to the Delta mutant in BCG-RV highlighted greater immune response breadth. Mechanistically, these BCG adjuvant effects were associated with elevated markers of trained immunity, including higher IL-1β and TNF-α expression in CD14+HLA-DR+monocytes and changes in chromatin accessibility highlighting BCG-induced epigenetic changes. This study provides first in-depth analysis of both antibody and memory T-cell responses induced by COVISHIELD™ in SARS-CoV-2 seronegative young adults in India with strong evidence of a BCG-induced booster effect and therefore a rational basis to validate BCG, a low-cost and globally available vaccine, as an adjuvant to enhance heterologous adaptive immune responses to current and emerging COVID-19 vaccines. Copyright © 2022 Rakshit, Adiga, Ahmed, Parthiban, Chetan Kumar, Dwarkanath, Shivalingaiah, Rao, D’Souza, Dias, Maguire, Doores, Zoodsma, Geckin, Dasgupta, Babji, van Meijgaarden, Joosten, Ottenhoff, Li, Netea, Stuart, De Rosa, McElrath and Vyakarnam.

Item Type: Journal Article
Publication: Frontiers in Immunology
Publisher: Frontiers Media S.A.
Additional Information: The copyright for this article belongs to the Author(s).
Keywords: BCG vaccine; immunological adjuvant; interleukin 2; tumor necrosis factor, chromatin; human; immunity; newborn; prevention and control; vaccination; young adult, Adjuvants, Immunologic; BCG Vaccine; Chromatin; COVID-19; COVID-19 Vaccines; Humans; Immunity; Infant, Newborn; Interleukin-2; SARS-CoV-2; Tumor Necrosis Factor-alpha; Vaccination; Young Adult
Department/Centre: Division of Biological Sciences > Centre for Infectious Disease Research
Date Deposited: 09 Nov 2022 05:41
Last Modified: 09 Nov 2022 05:41
URI: https://eprints.iisc.ac.in/id/eprint/77819

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