ISSN Print 2500–1094
ISSN Online 2542–1204
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)
ORIGINAL RESEARCH
Impact of untranslated mRNA sequences on immunogenicity of mRNA vaccines against M. tuberculosis in mice
About authors
1 Central Tuberculosis Research Institute, Moscow, Russia
2 Sirius University of Science and Technology, Sochi, Russia
3 Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia
Correspondence should be addressed: Galina S. Shepelkova
Jauzskaja alleja, 2, 107564, Moscow, Russia; ur.irtc@avoklepehs.g
About paper
Funding: the study was supported by the Ministry of Science and Higher Education of the Russian Federation (agreement No. 075-10-2021-113, project ID RF---193021X0001).
Acknowledgements: the authors express their gratitude to staff members of the Sirius University of Science and Technology: I.M. Terenin for in vitro transcription, O.V. Zaborova for mRNA formulation into lipid nanoparticles.
Author contribution: Shepelkova GS — planning the experiments and experimental procedure (in vivo and ex vivo), data analysis, manuscript writing; Reshetnikov VV — cloning, mRNA vaccine preparation, manuscript writing; Avdienko VG — experimental procedure (in vivo and ex vivo), data analysis; Sheverev DV — mRNA vaccine preparation, data analysis; Yeremeev VV — study design, data analysis, manuscript writing; Ivanov RA — study design, manuscript writing.
Compliance with ethical standards: the study was approved by the Ethics Committee of the Central Tuberculosis Research Institute (protocol № 3/2 dated 11 May 2023) 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: 2023-11-17
Accepted: 2023-12-19
Published online: 2023-12-31
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Fig. 1. Experimental design
Fig. 2. Adaptive immune response induction by mRNA vaccines. В6 mice were immunized twice (42 and 21 days before the experiment) with mRNA vaccines. BCG immunization was performed 35 days before the experiment. On the day of experiment, IFN-producing cell counts were determined in responders to mycobacterial antigens (А), as well as the delayed hypersensitivity reaction (B) and production of specific antibodies against mycobacterial antigens (C). Means ± SEM are presented, where n — five mice per group for А and C, eight mice per group for B. А, B. * — p < 0.05; * * — p < 0.01; * * * — p < 0.001 compared to control. C. * — significant difference from control for BCG, Δ — significant difference from control for 5'-Mod-Esat6-3'-Mod vaccine, ● — significant difference from control for 5'-Rabb-Esat6-3'-EMCV vaccine, ■ — significant difference from control for 5'-TLP-Esat6-3'-Mod vaccine
Fig. 3. Protective immune response associated with immunization with mRNA vaccines. I/St mice were immunized twice (42 and 21 days before the experiment) with mRNA vaccines. BCG immunization was performed 35 days before the experiment. Mice were infected with the M. tuberculosis virulent strain in a dose of 500,000 CFU/mouse. Mycobacterial load in the spleen (А) and the lungs (B) of infected animals was assessed 50 days later, along with the dynamic changes in the mouse death rate after infection (C). Means ± SEM are presented, where n – five (А, B) and eight (C) mice per group; * — p < 0.05; * * — p < 0.01; * * * — p < 0.001
