Development of a subunit vaccine against virus of african svine virus based on cd2v protein with immunoinformatics and molecular dynamics methods

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Abstract

A subunit vaccine against the African swine fever virus (ASF) has been designed using immunoinformatics and molecular dynamics methods. The three-dimensional structure of the selected immunogenic protein of the ASF-CD2v virus was modelled, and its topology relative to the membrane was predicted. B- and T-cell epitopes for the supramembrane part of CD2v were predicted, and their immunogenicity, allergenicity, and toxicity were evaluated. In order to facilitate the development of a subunit vaccine, the least variable site was identified on the basis of an analysis of the conservatism of the predicted epitopes. The stability of the selected supramembrane site in an aqueous salt solution was evaluated using molecular dynamics methods, and it was demonstrated that the site is structurally stable. The immunomodulation method has demonstrated that the developed candidate vaccine is capable of eliciting a sustained immune response and does not result in the development of a cytokine storm.

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About the authors

A. S. Ivanovsky

Shubnikov Institute of Crystallography of Kurchatov Complex of Crystallography and Photonics of NRC “Kurchatov Institute; MIREA-Russian Technology University

Author for correspondence.
Email: a.1wanowskiy@gmail.com
Russian Federation, Moscow; Moscow

V. I. Timofeev

Shubnikov Institute of Crystallography of Kurchatov Complex of Crystallography and Photonics of NRC “Kurchatov Institute

Email: a.1wanowskiy@gmail.com
Russian Federation, Moscow

A. V. Kalach

MIREA-Russian Technology University

Email: a.1wanowskiy@gmail.com
Russian Federation, Moscow

Y. V. Kordonskaya

National Research Centre “Kurchatov Institute”

Email: a.1wanowskiy@gmail.com
Russian Federation, Moscow

M. A. Marchenkova

Shubnikov Institute of Crystallography of Kurchatov Complex of Crystallography and Photonics of NRC “Kurchatov Institute

Email: a.1wanowskiy@gmail.com
Russian Federation, Moscow

Y. V. Pisarevsky

Shubnikov Institute of Crystallography of Kurchatov Complex of Crystallography and Photonics of NRC “Kurchatov Institute

Email: a.1wanowskiy@gmail.com
Russian Federation, Moscow

Y. A. Dyakova

National Research Centre “Kurchatov Institute”

Email: a.1wanowskiy@gmail.com
Russian Federation, Moscow

M. V. Kovalchuk

Shubnikov Institute of Crystallography of Kurchatov Complex of Crystallography and Photonics of NRC “Kurchatov Institute; National Research Centre “Kurchatov Institute”

Email: a.1wanowskiy@gmail.com
Russian Federation, Moscow; Moscow

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Supplementary files

Supplementary Files
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2. Fig. 1. Spatial structure of the CD2v protein with marked subdomains. Color shows the topology relative to the membrane: blue – supramembrane part, red – membrane, pink – submembrane part.

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3. Fig. 2. The location of the protein relative to the cell membrane.

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4. Fig. 3. Spatial structure of the supramembrane domain of the CD2v protein. The localization of the predicted T-line epitopes is marked in light color.

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5. Fig. 4. Spatial structure of the supramembrane B-subdomain of the CD2v protein. The localization of the predicted B-linear epitopes is marked in light color.

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6. Fig. 5. Antibodies and immunoglobulins. Antibodies are divided by isotype (a). Cytokines. Concentration of cytokines and interleukins. D in the inset is a cytokine storm danger signal (b). Total number of B-lymphocytes, memory cells and their division into isotypes (c). Number of B-lymphocytes in blood plasma, divided into isotypes (d). Total number of T-helper lymphocytes and memory cells (e). Total number of T-regulatory lymphocytes, active cells and memory cells (e). Macrophages. Total number, internalized, representing the major histocompatibility complex class II, active and resting macrophages (g).

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7. Fig. 6. Radius of gyration of the vaccine candidate during molecular dynamics simulation.

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8. Fig. 7. Standard deviation of candidate vaccine atoms during molecular dynamics simulation.

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9. Fig. 8. Root mean square fluctuation (RMS) of amino acid residues of the vaccine during molecular dynamics.

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