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

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• Epidemiological studies and clinical trials indicate the Bacillus Calmette-Guérin (BCG) vaccine offers protection against coronavirus disease 2019 (COVID-19).
• Over 30 clinical trials are investigating BCG's potential to prevent or mitigate COVID-19 severity.
• The precise immunological mechanism underlying BCG's protective effect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains undetermined.

Purpose of the Study:

• To elucidate the mechanism by which BCG vaccination may induce SARS-CoV-2-specific T cell responses.
• To identify specific BCG-derived peptides that share sequence homology with SARS-CoV-2 proteins.
• To demonstrate the ability of BCG-primed T cells to recognize SARS-CoV-2 peptides.

Main Methods:

• Identification of 8 novel BCG-derived peptides exhibiting significant sequence homology to SARS-CoV-2 NSP3 or NSP13.
• Utilizing an in vitro co-culture system to assess T cell responses.
• Priming human CD4+ and CD8+ T cells with BCG-derived peptides and evaluating their reactivity to homologous SARS-CoV-2 peptides.

Main Results:

• BCG-derived peptides were identified with sequence homology to SARS-CoV-2 proteins.
• Human CD4+ and CD8+ T cells primed in vitro with BCG-derived peptides demonstrated enhanced reactivity to corresponding SARS-CoV-2 peptides.
• Despite HLA polymorphism, all 20 individuals showed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2 peptides after BCG peptide priming.

Conclusions:

• This study provides an in vitro mechanism potentially explaining the epidemiological observations of BCG-conferred protection against COVID-19.
• BCG vaccination may induce cross-reactive T cell responses against SARS-CoV-2 through shared peptide epitopes.
• The findings highlight the role of T cell immunity in the context of BCG's potential prophylactic effects against COVID-19.