Frontiers in Immunology (Aug 2021)

BCG Vaccine Derived Peptides Induce SARS-CoV-2 T Cell Cross-Reactivity

  • Peter J. Eggenhuizen,
  • Boaz H. Ng,
  • Janet Chang,
  • Ashleigh L. Fell,
  • Rachel M. Y. Cheong,
  • Wey Y. Wong,
  • Poh-Yi Gan,
  • Poh-Yi Gan,
  • Stephen R. Holdsworth,
  • Stephen R. Holdsworth,
  • Joshua D. Ooi

DOI
https://doi.org/10.3389/fimmu.2021.692729
Journal volume & issue
Vol. 12

Abstract

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Epidemiological studies and clinical trials suggest Bacillus Calmette-Guérin (BCG) vaccine has protective effects against coronavirus disease 2019 (COVID-19). There are now over 30 clinical trials evaluating if BCG vaccination can prevent or reduce the severity of COVID-19. However, the mechanism by which BCG vaccination can induce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses is unknown. Here, we identify 8 novel BCG-derived peptides with significant sequence homology to either SARS-CoV-2 NSP3 or NSP13-derived peptides. Using an in vitro co-culture system, we show that human CD4+ and CD8+ T cells primed with a BCG-derived peptide developed enhanced reactivity to its corresponding homologous SARS-CoV-2-derived peptide. As expected, HLA differences between individuals meant that not all persons developed immunogenic responses to all 8 BCG-derived peptides. Nevertheless, all of the 20 individuals that were primed with BCG-derived peptides developed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2-derived peptides. These findings provide an in vitro mechanism that may account, in part, for the epidemiologic observation that BCG vaccination confers some protection from COVID-19.

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