{"doi":"10.3389/fimmu.2022.985938","title":"Evidence for the heterologous benefits of prior BCG vaccination on COVISHIELD™ vaccine-induced immune responses in SARS-CoV-2 seronegative young Indian adults","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.","journal":"Frontiers in Immunology","year":2022,"id":247083,"datarank":0.5375278407684165,"base_score":3.58351893845611,"endowment":3.58351893845611,"self_citation_contribution":0.5375278407684165,"citation_network_contribution":0.0,"self_endowment_contribution":0.5375278407684165,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":647555,"name":"Vasista Adiga","orcid":"0000-0002-6996-4786","position":1,"is_corresponding":false},{"id":400197,"name":"Asma Ahmed","orcid":"0000-0001-8690-2264","position":2,"is_corresponding":false},{"id":884457,"name":"Chaitra Parthiban","orcid":"0000-0003-0998-7764","position":3,"is_corresponding":false},{"id":885128,"name":"Nirutha Chetan Kumar","orcid":null,"position":4,"is_corresponding":false},{"id":648742,"name":"Pratibha Dwarkanath","orcid":null,"position":5,"is_corresponding":false},{"id":885129,"name":"Sudarshan Shivalingaiah","orcid":null,"position":6,"is_corresponding":false},{"id":885130,"name":"Srishti Rao","orcid":null,"position":7,"is_corresponding":false},{"id":647557,"name":"George D′Souza","orcid":"0000-0003-0343-4675","position":8,"is_corresponding":false},{"id":647556,"name":"Mary Dias","orcid":"0000-0002-5313-1819","position":9,"is_corresponding":false},{"id":884458,"name":"Thomas J. 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