ORIGINAL RESEARCH
The candidate anti-tuberculosis mRNA vaccine immunogenicity and reactogenicity dependency on the animal’s sex and the vaccine dose
1 Sirius University of Science and Technology, Sirius, Russia
2 Central Tuberculosis Research Institute, Moscow, Russia
3 National Research Centre "Kurchatov Institute", Moscow, Russia
Correspondence should be addressed: Vasily V. Reshetnikov
Olimpiysky prospekt, 1, Sochi, 354340, Russia; ur.hepsuitnalat@vv.vokintehser
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 formulation of mRNA into lipid nanoparticles.
Author contribution: Reshetnikov VV — mRNA vaccine preparation, experimental procedure, manuscript writing; Shepelkova GS — experimental procedure, data analysis; Rybakova AV — experimental procedure, data analysis; Trashkov AP — planning the experiment, manuscript editing; Yeremeev VV — planning the experiment, manuscript editing; Ivanov RA — planning the experiment, manuscript editing.
Compliance with ethical standards: the study was approved by the Ethics Committee of the National Research Centre "Kurchatov Institute" (protocol No. 2 dated 31 October 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).
- Matarazzo L, Bettencourt PJG. mRNA vaccines: a new opportunity for malaria, tuberculosis and HIV. Front Immunol. 2023;14: 1172691.
- Kazakova A, Zhelnov P, Sidorov R, Rogova A, Vasileva O, et al. DNA and RNA vaccines against tuberculosis: a scoping review of human and animal studies Frontiers in Immunology. 2024; 15.
- Ndeupen S, Qin Z, Jacobsen S, Bouteau A, Estanbouli H, et al. The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory. iScience. 2021; 24: 103479.
- Pateev I, Seregina K, Ivanov R, Reshetnikov V. Biodistribution of RNA Vaccines and of Their Products: Evidence from Human and Animal Studies. Biomedicines. 2023; 12.
- Kirshina AKA, Kolosova E, Imasheva E, Vasileva O, Zaborova O, Terenin I, Muslimov A, Reshetnikov V. Effects of various mRNALNP vaccine doses on neuroinflammation in BALB/c mice. RSMU. 2022; 6.
- van den Ouweland F, Charpentier N, Tureci O, Rizzi R, Mensa FJ, et al. Safety and reactogenicity of the BNT162b2 COVID-19 vaccine: Development, post-marketing surveillance, and real-world data. Hum Vaccin Immunother. 2024; 20: 2315659.
- Pang APS, Higgins-Chen AT, Comite F, Raica I, Arboleda C, et al. Longitudinal Study of DNA Methylation and Epigenetic Clocks Prior to and Following Test-Confirmed COVID-19 and mRNA Vaccination. Front Genet. 2022; 13: 819749.
- European Medicines Agency. Moderna Assessment Report COVID-19 Vaccine Moderna. 2021.
- European Medicines Agency. Assessment report: Comirnaty. 2021.
- Jin Z, Wu J, Wang Y, Huang T, Zhao K, et al. Safety and immunogenicity of the COVID-19 mRNA vaccine CS-2034: A randomized, double-blind, dose-exploration, placebo-controlled multicenter Phase I clinical trial in healthy Chinese adults. J Infect. 2023; 87: 556–70.
- Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, et al. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N Engl J Med. 2020; 383: 1920–31.
- Walsh EE, Frenck RW, Jr, Falsey AR, Kitchin N, Absalon J, et al. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med. 2020; 383: 2439–50.
- Reshetnikov V, Terenin I, Shepelkova G, Yeremeev V, Kolmykov S, et al. Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis. Int J Mol Sci. 2024; 25.
- Vasileva O, Krapivin B, Muslimov A, Kukushkin I, Pateev I, Rybtsov S, 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.
- Teijaro JR, Farber DL. COVID-19 vaccines: modes of immune activation and future challenges. Nat Rev Immunol. 2021; 21: 195–7.
- Verbeke R, Hogan MJ, Lore K, Pardi N. Innate immune mechanisms of mRNA vaccines. Immunity. 2022; 55: 1993–2005.
- Muslimov A, Tereshchenko V, Shevyrev D, Rogova A, Lepik K, et al. The Dual Role of the Innate Immune System in the Effectiveness of mRNA Therapeutics. Int J Mol Sci. 2023; 24.
- Zhuang CL, Lin ZJ, Bi ZF, Qiu LX, Hu FF, et al. Inflammationrelated adverse reactions following vaccination potentially indicate a stronger immune response. Emerg Microbes Infect. 2021; 10: 365–75.
- Kang DD, Hou X, Wang L, Xue Y, Li H, et al. Engineering LNPs with polysarcosine lipids for mRNA delivery. Bioact Mater. 2024; 37: 86–93.
- Schinas G, Polyzou E, Dimakopoulou V, Tsoupra S, Gogos C, et al. Immune-mediated liver injury following COVID-19 vaccination. World J Virol. 2023; 12: 100–8.
- Flanagan KL, Fink AL, Plebanski M, Klein SL. Sex and Gender Differences in the Outcomes of Vaccination over the Life Course. Annu Rev Cell Dev Biol. 2017; 33: 577–99.
- Klein SL, Jedlicka A, Pekosz A. The Xs and Y of immune responses to viral vaccines. Lancet Infect Dis. 2010; 10: 338–49.
- Bignucolo A, Scarabel L, Mezzalira S, Polesel J, Cecchin E, et al. Sex Disparities in Efficacy in COVID-19 Vaccines: A Systematic Review and Meta-Analysis. Vaccines (Basel). 2021; 9.