Development of multi-epitope vaccines against the monkeypox virus based on envelope proteins using immunoinformatics approaches

Caixia Tan; Fei Zhu; Pinhua Pan; Anhua Wu; Chunhui Li

doi:10.3389/fimmu.2023.1112816

Development of multi-epitope vaccines against the monkeypox virus based on envelope proteins using immunoinformatics approaches

Front Immunol. 2023 Mar 13:14:1112816. doi: 10.3389/fimmu.2023.1112816. eCollection 2023.

Authors

Caixia Tan^{1

2}, Fei Zhu^{2

3

4

5

6}, Pinhua Pan^{2

3

4

5

6}, Anhua Wu^{1

2}, Chunhui Li^{1

2}

Affiliations

¹ Department of Infection Control Center of Xiangya Hospital, Central South University, Changsha, Hunan, China.
² National Clinical Research Center for Geriatric Disorder, Xiangya Hospital, Changsha, Hunan, China.
³ Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁵ Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China.
⁶ Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China.

Abstract

Background: Since May 2022, cases of monkeypox, a zoonotic disease caused by the monkeypox virus (MPXV), have been increasingly reported worldwide. There are, however, no proven therapies or vaccines available for monkeypox. In this study, several multi-epitope vaccines were designed against the MPXV using immunoinformatics approaches.

Methods: Three target proteins, A35R and B6R, enveloped virion (EV) form-derived antigens, and H3L, expressed on the mature virion (MV) form, were selected for epitope identification. The shortlisted epitopes were fused with appropriate adjuvants and linkers to vaccine candidates. The biophysical andbiochemical features of vaccine candidates were evaluated. The Molecular docking and molecular dynamics(MD) simulation were run to understand the binding mode and binding stability between the vaccines and Toll-like receptors (TLRs) and major histocompatibility complexes (MHCs). The immunogenicity of the designed vaccines was evaluated via immune simulation.

Results: Five vaccine constructs (MPXV-1-5) were formed. After the evaluation of various immunological and physicochemical parameters, MPXV-2 and MPXV-5 were selected for further analysis. The results of molecular docking showed that the MPXV-2 and MPXV-5 had a stronger affinity to TLRs (TLR2 and TLR4) and MHC (HLA-A*02:01 and HLA-DRB1*02:01) molecules, and the analyses of molecular dynamics (MD) simulation have further confirmed the strong binding stability of MPXV-2 and MPXV-5 with TLRs and MHC molecules. The results of the immune simulation indicated that both MPXV-2 and MPXV-5 could effectively induce robust protective immune responses in the human body.

Conclusion: The MPXV-2 and MPXV-5 have good efficacy against the MPXV in theory, but further studies are required to validate their safety and efficacy.

Keywords: immunoinformatics; molecular docking; molecular dynamics (MD) simulation; monkeypox virus (MPXV); multi-epitope vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Epitopes, T-Lymphocyte
Humans
Molecular Docking Simulation
Monkeypox virus*
Mpox (monkeypox)*
Vaccines, Subunit

Substances

Epitopes, T-Lymphocyte
Vaccines, Subunit

Grants and funding

This research was supported by the National Key Research and Development Program of China (No. 2022YFC2009801), the Natural Science Foundation of Hunan Province (No. 2021JJ31071), the National Clinical Research Center for Geriatric Disorders (Xiangya Hospital, No. 2021KFJJ05) and the Research Project on Education and Teaching Reform of Central South University (No. 2021 jy139-2). Health Development Research Center of the National Health Commission, "Evidence-based Evaluation and Demonstration Base Construction Project of Infection Control Measures in Healthcare Institutions"(CNHDRC-KJ-L-2020-53-04375).