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, Stephen R. Holdsworth, Joshua D. Ooi

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24 Citations (Scopus)


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.

Original languageEnglish
Article number692729
Number of pages12
JournalFrontiers in Immunology
Publication statusPublished - 5 Aug 2021


  • BCG
  • COVID-19
  • cross-protection
  • heterologous immunity
  • T cell
  • vaccine

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