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Rakshit, S.; Adiga, V.; Ahmed, A.; Parthiban, C.; Kumar, N.C.; Dwarkanath, P.; ... ; Vyakarnam, A. (2022)

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

Article / Letter to editor
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 (TM), an efficacious and the most widely distributed vaccine in India. We compared COVISHIELD (TM) 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 (TM) 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 (TM) booster, including distinct CD4+IFN-gamma+ and CD4+IFN-gamma- effector memory (EM) subsets co-expressing IL-2, TNF-alpha and activation induced markers (AIM) CD154/CD137 as well as CD8+IFN-gamma+ EM,TEMRA (T cell EM expressing RA) subset combinations co-expressing...Show moreThis 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 (TM), an efficacious and the most widely distributed vaccine in India. We compared COVISHIELD (TM) 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 (TM) 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 (TM) booster, including distinct CD4+IFN-gamma+ and CD4+IFN-gamma- effector memory (EM) subsets co-expressing IL-2, TNF-alpha and activation induced markers (AIM) CD154/CD137 as well as CD8+IFN-gamma+ EM,TEMRA (T cell EM expressing RA) subset combinations co-expressing TNF-alpha 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-1 beta and TNF-alpha 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 (TM) 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.Show less
BCG
SARS-CoV-2
T cell
antibodies
trained immunity
All authors
Rakshit, S.; Adiga, V.; Ahmed, A.; Parthiban, C.; Kumar, N.C.; Dwarkanath, P.; Shivalingaiah, S.; Rao, S.S.; D'Souza, G.; Dias, M.; Maguire, T.J.A.; Doores, K.J.; Zoodsma, M.; Geckin, B.; Dasgupta, P.; Babji, S.; Meijgaarden, K.E. van; Joosten, S.J.; Ottenhoff, T.H.M.; Li, Y.; Netea, M.G.; Stuart, K.D.; Rosa, S.C. de; McElrath, M.J.; Vyakarnam, A.
Date
2022-10-04
Journal
Frontiers in Immunology
Volume
13
DOI
doi:10.3389/fimmu.2022.985938