MULTIEPITOPE mRNA VACCINE mRNA-mEp21-FL-IDT PROVIDES EFFECTIVE PROTECTION AGAINST M. tuberculosis

Tuberculosis is a leading bacterial infection in terms of lethality. The development of new tuberculosis vaccines may reduce the number of new cases and deaths from it. One of the most promising areas of vaccination is represented by mRNA vaccines, which have already proven their high effectiveness against COVID-19 and other viral infections. In our study, we developed four new multiepitope mRNA antituberculosis vaccines by modern immunoinformatic methods; the vaccines differ from each other in sequences of encoded adjuvants and codon composition. Their immunogenicity and protectivity were tested in experiments on mice. Most of the developed mRNA vaccines have led to the formation of both cellular and humoral immunity. Meanwhile, the adaptive response was stronger in the case of vaccines with adjuvant RpfE. Nonetheless, the best protective response was elicited by the mRNA-mEp21-FL-IDT vaccine (with adjuvant FL), which decreased mycobacterial load in the lungs after infection of mice with M. tuberculosis and increased animal survival. Altogether, our results indicate that the mRNA-mEp21-FL-IDT vaccine, developed by mRNA immu-noinformatic methods, provides effective protection comparable to that seen after BCG vaccination.