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 .
|
PDF
fro_imm_13_2022.pdf - Published Version Download (14MB) | Preview |
Abstract
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 |
Actions (login required)
 |
View Item |
