Email this article IMMUNOCOMPETENT MICE AS A MODEL FOR PRECLINICAL STUDIES OF mRNA VACCINES IMMUNOGENICITY
- Authors: Shkurnikov M.Y.1, Tonevitskaya S.A.2, Stepanova E.V.2, Slobodov S.A.2
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Affiliations:
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
- Faculty of Biology and Biotechnology, HSE University
- Issue: Vol 512, No 1 (2023)
- Pages: 444-448
- Section: Articles
- URL: https://journals.rcsi.science/2686-7389/article/view/140846
- DOI: https://doi.org/10.31857/S2686738923600371
- EDN: https://elibrary.ru/OZROHS
- ID: 140846
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Abstract
Conducting preclinical studies of mRNA vaccines is complicated by the lack of relevant animal models of the human immune system. Immunocompetent mice are widely used in biomedical research. However, critical differences in the genetics and immune system of mice and humans prevent the study of unique human immune responses in mice. Within the framework of this work, the possibility of modeling the cytotoxic T-cell response to mRNA vaccines encoding the S-protein of the SARS-CoV-2 virus was investigated. High-affinity peptides from S-protein were analyzed for the most frequent allelic variants of human MHC-I, two immunocompetent mouse lines (C57BL/6, BALB/c) and an outbred mouse model of IRC. The results of computer modeling have shown that mouse models can be used in preclinical studies of mRNA vaccines against SARS-CoV-2. Mouse MHC-I is able to present virus peptides that are highly affine for human MHC-I. Moreover, the immunogenicity of some of them has already been confirmed by examining blood samples from patients who have had COVID-19.
Keywords
About the authors
M. Yu. Shkurnikov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Author for correspondence.
Email: mshkurnikov@hse.ru
Russian Federation, Moscow
S. A. Tonevitskaya
Faculty of Biology and Biotechnology, HSE University
Email: mshkurnikov@hse.ru
Russian Federation, Moscow
E. V. Stepanova
Faculty of Biology and Biotechnology, HSE University
Email: mshkurnikov@hse.ru
Russian Federation, Moscow
S. A. Slobodov
Faculty of Biology and Biotechnology, HSE University
Email: mshkurnikov@hse.ru
Russian Federation, Moscow
References
- Wang G. et al. mRNA produced by VSW-3 RNAP has high-level translation efficiency with low inflammatory stimulation // Cell Insight. 2022. V. 1. № 5. P. 100056.
- Inagaki M. et al. Cap analogs with a hydrophobic photocleavable tag enable facile purification of fully capped mRNA with various cap structures // Nat Commun. 2023. V. 14. № 1. P. 2657.
- Hasanzadeh A. et al. Could artificial intelligence revolutionize the development of nanovectors for gene therapy and mRNA vaccines? // Nano Today. 2022. V. 47. P. 101665.
- Kusnadi A. et al. Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells. // Science immunology. 2021. V. 6. № 55.
- Wherry E.J., Ahmed R. Memory CD8 T-Cell Differentiation during Viral Infection // Journal of Virology. American Society for Microbiology (ASM), 2004. V. 78. № 11. P. 5535–5545.
- Pérarnau B. et al. SingleH2Kb, H2Db and doubleH2KbDb knockout mice: peripheral CD8+ T cell repertoire and antilymphocytic choriomeningitis virus cytolytic responses // Eur. J. Immunol. 1999. V. 29. № 4. P. 1243–1252.
- Shkurnikov M. et al. HLA-A*01: 01 allele diminishing in COVID-19 patients population associated with non-structural epitope abundance in CD8+ T-cell repertoire // PeerJ. 2023. V. 11. P. e14707.
- Elbe S., Buckland-Merrett G. Data, disease and diplomacy: GISAID’s innovative contribution to global health // Global Challenges. 2017. V. 1. № 1. P. 33–46.
- Nielsen M. et al. The role of the proteasome in generating cytotoxic T-cell epitopes: Insights obtained from improved predictions of proteasomal cleavage // Immunogenetics. 2005. V. 57. № 1–2. P. 33–41.
- Reynisson B. et al. NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data // Nucleic acids research. 2020. V. 48. № W1. P. W449–W454.
- Visekruna A. et al. Comparative expression analysis and characterization of 20S proteasomes in human intestinal tissues: The proteasome pattern as diagnostic tool for IBD patients // Inflammatory Bowel Diseases. 2009. V. 15. № 4. P. 526–533.
- Nersisyan S. et al. Alterations in SARS-CoV-2 Omicron and Delta peptides presentation by HLA molecules // PeerJ. 2022. V. 10. P. e13354.
- Titov A. et al. Immunogenic epitope panel for accurate detection of non-cross-reactive T cell response to SARS-CoV-2 // JCI Insight. 2022. V. 7. № 9. P. e157699.
- Weingarten-Gabbay S. et al. Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs // Cell. 2021. V. 184. № 15. P. 3962–3980.e17.
- Xiao C. et al. SARS-CoV-2 variant B.1.1.7 caused HLA-A2+ CD8+ T cell epitope mutations for impaired cellular immune response // iScience. 2022. V. 25. № 3. P. 103934.
- Habel J.R. et al. Suboptimal SARS-CoV-2−specific CD8 + T cell response associated with the prominent HLA-A*02:01 phenotype // Proc. Natl. Acad. Sci. U.S.A. 2020. V. 117. № 39. P. 24384–24391.
- Nersisyan S. et al. T-CoV: a comprehensive portal of HLA-peptide interactions affected by SARS-CoV-2 mutations // Nucleic Acids Research. 2022. V. 50. № D1. P. D883–D887.
