Proof-of-Concept Study of Liposomes with a Set of SARS-CoV-2 Viral T-Cell Epitopes as a Vaccine

D. S. Tretiakova; Третьякова Д. С.; E. V. Svirshchevskaya; Свирщевская Е. В.; M. V. Konovalova; Коновалова М. В.; K. S. Plokhikh; Плохих К. С.; V. A. Kazakov; Казаков В. А.; G. B. Telegin; Телегин Г. Б.; A. S. Chernov; Чернов А. С.; V. A. Gushchin; Гущин В. А.; D. V. Vasina; Васина Д. В.; N. S. Egorova; Егорова Н. С.; I. A. Boldyrev; Болдырев И. А.; N. R. Onishchenko; Онищенко Н. Р.; A. S. Alekseeva; Алексеева А. С.; E. L. Vodovozova; Водовозова Е. Л.

doi:10.31857/S0132342322060252

Proof-of-Concept Study of Liposomes with a Set of SARS-CoV-2 Viral T-Cell Epitopes as a Vaccine

Autores: Tretiakova D.¹, Svirshchevskaya E.¹, Konovalova M.¹, Plokhikh K.², Kazakov V.³, Telegin G.³, Chernov A.³, Gushchin V.⁴, Vasina D.⁴, Egorova N.¹, Boldyrev I.¹, Onishchenko N.¹, Alekseeva A.¹, Vodovozova E.¹
Afiliações:
1. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
2. National Research Center “Kurchatov Institute”
3. Pushchino Branch of Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
4. Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Healthcare of the Russian Federation
Edição: Volume 49, Nº 1 (2023)
Páginas: 48-64
Seção: Articles
URL: https://journals.rcsi.science/0132-3423/article/view/145868
DOI: https://doi.org/10.31857/S0132342322060252
EDN: https://elibrary.ru/POMUEE
ID: 145868

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Resumo

Potential nonameric epitopes of CD8⁺ T lymphocytes were selected from the composition of structural, accessory, and non-structural proteins of SARS-CoV-2 virus (13 peptides) and a 15-mer epitope of CD4⁺ T lymphocytes, from the S-protein, based on the analysis of publications on genome-wide immunoinformatic analysis of T-cell epitopes of the virus (Wuhan strain), as well as a number of clinical studies of immunodominant epitopes among patients recovering from COVID-19 disease. The peptides were synthesized and five compositions of 6–7 peptides were included in liposomes from egg phosphatidylcholine and cholesterol (~200 nm size) obtained by extrusion. After double subcutaneous immunization of conventional mice, activation of cellular immunity was assessed by the level of cytokine synthesis by splenocytes in vitro in response to stimulation with relevant peptide compositions. Liposomal formulation exhibiting the best result in terms of the formation of specific cellular immunity in response to vaccination was selected for further experiments. Evaluation of the protective efficacy of this formulation in an infectious mouse model showed a positive trend in the frequency of occurrence of hyaline-like membranes in the lumen of the alveoli, as well as a somewhat lower severity of microcirculatory disorders. The latter circumstance can potentially help reduce the severity of the disease and prevent its adverse outcomes. A method to produce liposome preparations with peptide compositions for long-term storage is under development.

Palavras-chave

Т-cells, epitopes, SARS-CoV-2, vaccines, peptides, liposomes, cytokines

Bibliografia

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