Immunogenicity of full-length and multi-epitope mRNA vaccines for M. Tuberculosis as demonstrated by the intensity of T-cell response: a comparative study in mice

Vasileva OO1, Tereschenko VP1, Krapivin BN1, Muslimov AR1,2, Kukushkin IS1, Pateev II1, Rybtsov SA1, Ivanov RA1, Reshetnikov VV1,3
About authors

1 Translational Medicine Research Center, Sirius University of Science and Technology (Autonomous Non-Commercial Higher Education Organization), Sirius, Russia

2 Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia

3 Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia

Correspondence should be addressed: Vasily V. Reshetnikov
Olympiyskiy prospekt, 1, Sochi, 354340, Russia; ur.hepsuitnalat@vv.vokintehser

About paper

Funding: the study was supported by the Ministry of Science and Higher Education of the Russian Federation (agreement № 075-10-2021-113, unique project identifier RF----193021X0001).

Acknowledgements: the authors express their gratitude to the staff of the Sirius University: Terenin IM for in vitro transcription, Zaborova OV for the formulation of mRNA into lipid nanoparticles, Gavrilyak MA and Golovin EV for purification and characterization of the Rv3875 protein; Shevyrev DV for setting up the intracellular staining experiment and Sitikova VA for assistance in the context of the animal experiment.

Author contribution: Vasileva OO, Tereschenko VP — work with the cells, data analysis, article authoring, figures authoring; Krapivin BN, Pateev II, Rybtsov SA — work with the cells, animal experiment, data analysis; Muslimov AR, Kukushkin IS — design of structures, cloning; Ivanov RA, Reshetnikov VV — text editing, data analysis, project coordination.

Compliance with the ethical standards: animal study was approved by the Ethics Committee of the Institute of Cytology and Genetics (2022); carried out in accordance with the laboratory animals care guidelines (2010), Directive 2010/63/EU of the European parliament and of the Council on the protection of animals used for scientific purposes (2010), Good Laboratory Practice guidelines (2016).

Received: 2023-04-24 Accepted: 2023-06-15 Published online: 2023-06-29

Development of the new tuberculosis vaccines that would be effective in adults is an urgent task: worldwide, the annual death toll of this disease exceeds 1.5 million. In the recent decades, the matter has been addressed in numerous studies, but none has yielded an effective vaccine so far. There are many factors to resistance against tuberculosis; this study focuses on the T-cell response, a mechanism that enables elimination of intracellular pathogens, such as M. tuberculosis. We aimed to develop an mRNA vaccine capable of triggering a pronounced T-cell response to the M. tuberculosis antigens. The in silico analysis allowed us to select epitopes of the M. tuberculosis secreted protein ESAT6 (Rv3875) and design a multi-epitope mRNA vaccine thereon. We assessed the intensity of T-cell response in mice immunized with mRNA vaccines that encode a full-length or multi-epitope antigen. The results of this study in mice show that immunization with a multi-epitope mRNA vaccine produces twice as many IFNγ-secreting splenocytes in response to specific stimulation than immunization with an mRNA vaccine encoding the full-length protein. Thus, the developed multi-epitope mRNA vaccine can be an effective M. tuberculosis prevention agent the mode of action of which involves formation of a pronounced T-cell response.

Keywords: mRNA vaccine, multi-epitope vaccine, T-cell response, ELISpot