Immunity in Harmony: Utilizing Overlapping Epitopes for Tuberculosis and COVID-19 Protection

INTRODUCTION: The BCG vaccine, widely administered against tuberculosis, has also been linked to reduced incidence of bacterial and viral infections, particularly those affecting the respiratory tract. Its antigens enhance innate immune responses and contribute to therapeutic effects, such as those observed in bladder cancer. Notably, reduced COVID-19 incidence has been reported in BCG-vaccinated populations from TB-endemic regions. METHODS: To investigate this hypothesis, immunoinformatics tools were employed to identify overlapping CD4, CD8, and B-cell epitopes shared between Mycobacteria and SARS-CoV-2. The most promising CD8 epitope was synthesized using the SPPS-Fmoc method, and antigen-specific Tcell proliferation was evaluated by CFSE dye-dilution assay. Additionally, the expression of proand anti-inflammatory molecules was assessed using qRT-PCR. RESULTS: Multiple overlapping T-cell and B-cell epitopes were identified between Mycobacteria and SARS-CoV-2. The T-cell epitopes displayed promiscuous binding characteristics, high immunogenicity, and strong affinity for both HLA class I and class II alleles. Experimental validation using the most immunodominant T-cell epitope confirmed its ability to induce proliferation and differentiation of T cells isolated from COVID-19-vaccinated individuals. DISCUSSION: The overlapping T-cell and B-cell epitopes identified through this approach may provide broader and more robust protection than initial exposure to virus-specific antigens, which the immune system encounters for the first time during infection or vaccination. This strategy may therefore support the rapid and effective development of future vaccines, particularly against emerging pathogens. CONCLUSION: The findings suggest that the higher level of protection observed in TB-endemic countries during recent pandemics may be attributable to cross-reactive mycobacterial antigens that stimulate protective immunity.