2023 / 06

Next Paper
DOI: 10.24075/brsmu.2023.054

ORIGINAL RESEARCH

Impact of untranslated mRNA sequences on immunogenicity of mRNA vaccines against M. tuberculosis in mice

Shepelkova GS1, Reshetnikov VV2,3, Avdienko VG1, Sheverev DV2, Yeremeev VV1, Ivanov RA2
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
|
  1. Global tuberculosis report, 2023.
  2. Lai R, Ogunsola AF, Rakib T, Behar SM. Key advances in vaccine development for tuberculosis-success and challenges. NPJ vaccines. 2023; 8: 158. DOI: 10.1038/s41541-023-00750-7.
  3. Self WH, Tenforde MW, Rhoads JP, Gaglani M, Ginde AA, Douin DJ, et al. Comparative Effectiveness of Moderna, PfizerBioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions — United States, MarchAugust 2021. MMWR. Morbidity and mortality weekly report. 2021; 70: 1337–43, DOI: 10.15585/mmwr.mm7038e1.
  4. Melo A, de Macedo LS, Invencao M, de Moura IA, da Gama M, de Melo CML, et al. Third-generation vaccines: features of nucleic acid vaccines and strategies to improve their efficiency. Genes. 2022; 13. DOI:10.3390/genes13122287.
  5. Martinon F, Krishnan S, Lenzen G, Magne R, Gomard E, Guillet JG, et al. Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA. European journal of immunology. 1993; 23: 1719–22, DOI: 10.1002/eji.1830230749.
  6. Conry RM, LoBuglio AF, Wright M, Sumerel L, Pike MJ, Johanning F, et al. Characterization of a messenger RNA polynucleotide vaccine vector. Cancer research. 1995; 55: 1397–400.
  7. Anderson BR, Muramatsu H, Jha BK, Silverman RH, Weissman D, Kariko K. Nucleoside modifications in RNA limit activation of 2'–5'-oligoadenylate synthetase and increase resistance to cleavage by RNase L. Nucleic acids research. 2011; 39: 9329– 38. DOI: 10.1093/nar/gkr586.
  8. Muslimov A, Tereshchenko V, Shevyrev D, Rogova A, Lepik K, Reshetnikov V, et al. The dual role of the innate immune system in the effectiveness of mRNA therapeutics. International journal of molecular sciences. 2023; 24. DOI: 10.3390/ijms241914820.
  9. Weng Y, Li C, Yang T, Hu B, Zhang M, Guo S, et al. The challenge and prospect of mRNA therapeutics landscape. Biotechnology advances. 2020; 40: 107534. DOI: 10.1016/j.biotechadv.2020.107534.
  10. Orlandini von Niessen AG, Poleganov MA, Rechner C, Plaschke A, Kranz LM, Fesser S, et al. Improving mRNA-based therapeutic gene delivery by expression-augmenting 3' UTRs identified by cellular library screening. Molecular therapy: the journal of the American Society of Gene Therapy. 2019; 27: 824–36. DOI: 10.1016/j.ymthe.2018.12.011.
  11. Cao J, Novoa EM, Zhang Z, Chen WCW, Liu D, Choi GCG, et al. High-throughput 5' UTR engineering for enhanced protein production in non-viral gene therapies. Nature communications. 2021; 12: 4138. DOI: 10.1038/s41467-021-24436-7.
  12. Vasileva O, Tereschenko TV, Krapivin B, Muslimov A, Kukushkin I, Pateev I, et al. 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. Bulletin of RSMU. 2023; 03: 42–48. DOI: 10.24075/brsmu.2023.021.
  13. Kirshina AS, Kazakova AA, Kolosova ES, Imasheva EA, Vasileva OO, Zaborova OV, et al. Effects of various mRNA-LNP vaccine doses on neuroinflammation in BALB/c mice. Bulletin of RSMU. 2022; 6. DOI: 10.24075/brsmu.2022.068.
  14. Avdienko VG, Babaian SS, Guseva AN, Kondratiuk NA, Rusakova LI, Averbakh MM, et al. Quantitative, spectral, and serodiagnostic characteristics of antimycobacterial IgG, IgM, and IgA antibodies in patients with pulmonary tuberculosis. Problemy tuberkuleza i boleznei legkikh. 2006; 47–55.
  15. Nikonenko BV, Apt AS, Mezhlumova MB, Avdienko VG, Yeremeev VV, Moroz AM. Influence of the mouse Bcg, Tbc-1 and xid genes on resistance and immune responses to tuberculosis infection and efficacy of bacille Calmette-Guerin (BCG) vaccination. Clinical and experimental immunology. 1996; 104: 37–43, DOI: 10.1046/j.1365-2249.1996.d01-643.x.
  16. Kozlova IV, Avdienko VG, Babayan SS, Andrievskaya IYu, Gergert VY. Diagnosis of Bactec samples by immunoglobulins of mouse hyperimmune sera obtained against modified antigens of the cell wall of Mycobacterium tuberculosis. Tuberculosis and Lung Diseases. 2019; 97: 25–30.
  17. Rijnink WF, Ottenhoff THM, Joosten SA. B-Cells and Antibodies as Contributors to Effector Immune Responses in Tuberculosis. Frontiers in immunology. 2021; 12: 640168. DOI: 10.3389/fimmu.2021.640168.
  18. Logan J, Shenk T. Adenovirus tripartite leader sequence enhances translation of mRNAs late after infection. Proceedings of the National Academy of Sciences of the United States of America. 1984; 81: 3655–9. DOI: 10.1073/pnas.81.12.3655.
  19. Kaufman RJ. Identification of the components necessary for adenovirus translational control and their utilization in cDNA expression vectors. Proceedings of the National Academy of Sciences of the United States of America. 1985; 82: 689–93. DOI: 10.1073/pnas.82.3.689.
  20. Sample PJ, Wang B, Reid DW, Presnyak V, McFadyen IJ, Morris DR, et al. Human 5' UTR design and variant effect prediction from a massively parallel translation assay. Nature biotechnology. 2019; 37: 803–9. DOI: 10.1038/s41587-019-0164-5.
  21. Kozak M. Features in the 5' non-coding sequences of rabbit alpha and beta-globin mRNAs that affect translational efficiency. Journal of molecular biology. 1994; 235: 95–110. DOI: 10.1016/s0022-2836(05)80019-1.
  22. Kumari S, Bugaut A, Huppert JL, Balasubramanian S. An RNA G-quadruplex in the 5' UTR of the NRAS proto-oncogene modulates translation. Nature chemical biology. 2007; 3: 218–21. DOI: 10.1038/nchembio864.