BCG-derived peptides induce T cell cross-reactivity to Sars-CoV-2 homologues

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently-discovered beta coronavirus capable of infecting humans and causing Coronavirus Disease 2019 (COVID-19). COVID-19 causes a variety of pathologies that are still being understood. While vaccines specific for COVID-19 are being developed and deployed throughout the world, another vaccine called Bacillus Calmette–Guérin (BCG) vaccine is being trialled to test whether it has a protective effect against COVID-19. Epidemiological studies have identified a negative correlation between BCG vaccination regime and COVID-19 severity and mortality. However, the mechanism by which a vaccine for a bacterium can protect against a virus is not well understood. Here we have identified a number of homologous peptide sequences shared between BCG and SARS-CoV-2. Using in vitro human T cell recall assays, we found that pre-sensitisation to BCG-derived peptides can induce T cell cross-reactivity to SARS-CoV-2 peptides. These findings assist in explaining the molecular mechanism behind the protective effect conferred by BCG vaccination in COVID-19, and supports the clinical trials exploring BCG vaccine as an integral part of the global effort to vaccinate against COVID-19.