Copyright: © 2025 by the authors. Licensee: Pirogov University.
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ORIGINAL RESEARCH

Comparison of the efficacy of mRNA vaccines against M. tuberculosis based on linear and circular RNAs

Kirshina AS1, Shepelkova GS2, Khlebnikova AS1, Maslov AA1, Kozlova AV1, Kunyk DA1, Yeremeev VV2, Ivanov RA1, Reshetnikov VV1
About authors

1 Sirius University of Science and Technology, Sirius, Russia

2 Central Tuberculosis Research Institute, Moscow, Russia

Correspondence should be addressed: Vasily V. Reshetnikov
Olimpiysky prospekt, 1, Sochi, 354340, Russia; ur.hepsuitnalat@vv.vokintehser, Vladimir V. Yeremeev, Yauzskaya alleya, 2, Moscow, 107564; Russia; ur.liam@65veemerey

About paper

Funding: the study was conducted within the framework of the State Assignment of the Central Tuberculosis Research Institute, R&D project: FURE-2025-0018.

Acknowledgements: the authors express their gratitude to O.V. Zaborova, staff member of the Sirius University of Science and Technology, for formulation of mRNA into lipid nanoparticles and E.I. Chebanyuk, staff member of the biotechnology laboratory of the Central Tuberculosis Research Institute, for assistance in animal handling and setting the experiments involving lineal mice.

Author contribution: Kirshina AS, Khlebnikova AS — mRNA vaccine preparation, planning the experiment, manuscript writing; Kozlova AV, Kunyk DA, Maslov AA — mRNA vaccine preparation; Shepelkova GS — experimental procedure, data analysis; Yeremeev VV, Ivanov RA — planning the experiment, manuscript editing; Reshetnikov VV — mRNA vaccine preparation, planning the experiment, manuscript editing.

Compliance with ethical standards: the study was approved by the Ethics Committee of the Central Tuberculosis Research Institute (protocol No. 3/2 dated 11 May 2022) and conducted in accordance with the Order of the Ministry of Health No. 755 and the Guidelines issued by the Office of Laboratory Animal Welfare (А5502-01).

Received: 2025-07-22 Accepted: 2025-08-17 Published online: 2025-08-26
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Fig. 1. mRNA vaccine immunogenicity assessment. А. Structure of the tuberculosis RNA vaccines with the MTB-mEp-5-1 antigen sequence based on the linear and circular RNAs. B. Experimental design scheme. C. Titer of IgG immunoglobulins to M. tuberculosis antigens in blood serum of mice after immunization with the tuberculosis vaccines. D. Differences in IPC counts in the spleen of mice vaccinated with various mRNA vaccine variants. The data are presented as the mean ± standard deviation. Mice per group n = 5. * — p < 0.05; * * — p < 0.01; * * * — p < 0.001; * * * * — p < 0.0001.
Fig. 2. Protective immune response assessment after immunization with mRNA vaccines. А. Experimental design scheme. B. Bacterial load in the lung tissue and the spleen of immunized mice (n = 5) after the M. tuberculosis infection (H37Rv strain). The data are presented as the mean ± standard deviation. C. Survival dynamics of mice (n = 10) immunized with tuberculosis vaccines after the M. tuberculosis infection (H37Rv strain). * — p < 0.05; * * — p < 0.01.
Table. Summary of study results