Multiepitope mRNA Vaccine mRNA-mEp21-FL-IDT Provides Efficient Protection against M. tuberculosis

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Alisa A. Kazakova¹, Galina S. Shepelkova², Ivan S. Kukushkin¹, Vladimir V. Yeremeev², Roman A. Ivanov¹, and Vasiliy V. Reshetnikov^1,a*

¹Sirius University of Science and Technology, 354340 Sirius Federal Territory, Russia

²Central Tuberculosis Research Institute, 107564 Moscow, Russia

^* To whom correspondence should be addressed.

Received: January 18, 2025; Revised: June 9, 2025; Accepted: June 9, 2025

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Tuberculosis is a leading cause of death from a bacterial infection agent. The development of new tuberculosis vaccines can reduce the number of new cases and tuberculosis-related deaths. One of the most promising areas in vaccination is development of mRNA vaccines, which have already proven their high effectiveness against COVID-19 and other viral infections. Using modern immunoinformatic methods, we developed four new antituberculosis multiepitope mRNA vaccines differing in the encoded adjuvants and codon composition and tested their immunogenicity and protectivity in mice. Most of the developed mRNA vaccines induced the formation of both cellular and humoral immunity. The adaptive response was stronger for the vaccines with the RpfE adjuvant; however, the best protective response was elicited by the mRNA-mEp21-FL-IDT vaccine with the FL adjuvant. This vaccine reduced the mycobacterial load in the lungs of mice infected with Mycobacterium tuberculosis and increased their survival rate. Altogether, our results indicate that the mRNA-mEp21-FL-IDT vaccine ensures effective protection against tuberculosis comparable to that provided by the BCG vaccine.

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KEY WORDS: mRNA vaccine, tuberculosis, multiepitope vaccines, molecular adjuvants, adaptive immunity, protective immunity

DOI: 10.1134/S0006297925600073

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