Frontiers in Immunology (Oct 2022)
Evidence for the heterologous benefits of prior BCG vaccination on COVISHIELD™ vaccine-induced immune responses in SARS-CoV-2 seronegative young Indian adults
- Srabanti Rakshit,
- Srabanti Rakshit,
- Vasista Adiga,
- Vasista Adiga,
- Vasista Adiga,
- Asma Ahmed,
- Asma Ahmed,
- Chaitra Parthiban,
- Chaitra Parthiban,
- Nirutha Chetan Kumar,
- Nirutha Chetan Kumar,
- Pratibha Dwarkanath,
- Sudarshan Shivalingaiah,
- Srishti Rao,
- George D’Souza,
- Mary Dias,
- Thomas J. A. Maguire,
- Katie J. Doores,
- Martijn Zoodsma,
- Martijn Zoodsma,
- Busranur Geckin,
- Prokar Dasgupta,
- Sudhir Babji,
- Krista E. van Meijgaarden,
- Simone A. Joosten,
- Tom H. M. Ottenhoff,
- Yang Li,
- Yang Li,
- Mihai G. Netea,
- Kenneth D. Stuart,
- Stephen C. De Rosa,
- M. Juliana McElrath,
- M. Juliana McElrath,
- Annapurna Vyakarnam,
- Annapurna Vyakarnam,
- Annapurna Vyakarnam
Affiliations
- Srabanti Rakshit
- Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India
- Srabanti Rakshit
- Infectious Disease Unit, St. John’s Research Institute, Bangalore, India
- Vasista Adiga
- Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India
- Vasista Adiga
- Infectious Disease Unit, St. John’s Research Institute, Bangalore, India
- Vasista Adiga
- Department of Biotechnology, PES University, Bangalore, India
- Asma Ahmed
- Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India
- Asma Ahmed
- Infectious Disease Unit, St. John’s Research Institute, Bangalore, India
- Chaitra Parthiban
- Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India
- Chaitra Parthiban
- Infectious Disease Unit, St. John’s Research Institute, Bangalore, India
- Nirutha Chetan Kumar
- Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India
- Nirutha Chetan Kumar
- Infectious Disease Unit, St. John’s Research Institute, Bangalore, India
- Pratibha Dwarkanath
- Department of Biotechnology, PES University, Bangalore, India
- Sudarshan Shivalingaiah
- Infectious Disease Unit, St. John’s Research Institute, Bangalore, India
- Srishti Rao
- Infectious Disease Unit, St. John’s Research Institute, Bangalore, India
- George D’Souza
- Division of Nutrition, St. John’s Research Institute, Bangalore, India
- Mary Dias
- Infectious Disease Unit, St. John’s Research Institute, Bangalore, India
- Thomas J. A. Maguire
- Department of Pulmonary Medicine, St. John’s Medical College, Bangalore, India
- Katie J. Doores
- Department of Pulmonary Medicine, St. John’s Medical College, Bangalore, India
- Martijn Zoodsma
- Department of Infectious Diseases, School of Immunology and Microbial Sciences, King’s College London, London, United Kingdom
- Martijn Zoodsma
- Department of Computational Biology for Individualized Infection Medicine, Centre for Individualized Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
- Busranur Geckin
- TWINCORE, a joint venture between the Helmholtz Centre for Infection Research, (HZI) and the Hannover Medical School (MHH), Hannover, Germany
- Prokar Dasgupta
- Department of Internal Medicine and Radboud Center for infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Sudhir Babji
- 0Peter Gorer Department of Immunobiology, Liver Renal Urology Transplant Gastro/Gastrointestinal Surgery, Inflammation Biology, King’s College London, London, United Kingdom
- Krista E. van Meijgaarden
- 1The Wellcome Trust Research Laboratory, Christian Medical College, Vellore, India
- Simone A. Joosten
- 1The Wellcome Trust Research Laboratory, Christian Medical College, Vellore, India
- Tom H. M. Ottenhoff
- 1The Wellcome Trust Research Laboratory, Christian Medical College, Vellore, India
- Yang Li
- Department of Infectious Diseases, School of Immunology and Microbial Sciences, King’s College London, London, United Kingdom
- Yang Li
- Department of Computational Biology for Individualized Infection Medicine, Centre for Individualized Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
- Mihai G. Netea
- TWINCORE, a joint venture between the Helmholtz Centre for Infection Research, (HZI) and the Hannover Medical School (MHH), Hannover, Germany
- Kenneth D. Stuart
- 2Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands
- Stephen C. De Rosa
- 3Centre for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, WA, United States
- M. Juliana McElrath
- 3Centre for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, WA, United States
- M. Juliana McElrath
- 4Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Centre, Seattle, WA, United States
- Annapurna Vyakarnam
- Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India
- Annapurna Vyakarnam
- Infectious Disease Unit, St. John’s Research Institute, Bangalore, India
- Annapurna Vyakarnam
- 5Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States
- DOI
- https://doi.org/10.3389/fimmu.2022.985938
- Journal volume & issue
-
Vol. 13
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.
Keywords
