In silico development of a novel anti-mutation, multi-epitope mRNA vaccine against MPXV variants of emerging lineage and sub-lineages by using immunoinformatics approaches

Abstract

Over the past year, an unexpected surge in human monkeypox (hMPX) cases has been observed. This outbreak differs from previous ones, displaying distinct epidemiological characteristics and transmission patterns, believed to be influenced by a newly emerging monkeypox virus (MPXV) lineage. Notably, this emerging MPXV lineage has exhibited several non-synonymous mutations, some of which are linked to immunomodulatory activities and antigenic characteristics that aid in host detection. However, specific treatments or vaccines for human monkeypox are currently lacking. Hence, we aim to develop a multi-epitope mRNA vaccine by using immunoinformatics approaches against the MPXV, particularly its emerging variants. Six proteins (A29L, A35R, B6R, M1R, H3L, and E8L) were chosen for epitope and mutation site identification. Seventeen top-performing epitopes and eight epitopes containing mutation sites were selected and combined with adjuvants, the PADRE sequence, and linkers for vaccine development. The molecular and physical properties of the designed vaccine (WLmpx) were favorable. Immunological characteristics of WLmpx were assessed through molecular docking, molecular dynamics (MD) simulations, and immune simulations. Finally, the vaccine sequence was utilized to formulate an mRNA-based vaccine. The informatics-based predicted results indicated that the designed vaccine exhibits significant potential in eliciting high-level humoral and cellular immune responses, but further validation through in vivo and vitro studies is warranted.

Communicated by Ramaswamy H. Sarma

Keywords:

• Monkeypox virus (MPXV)
• mRNA vaccine
• anti-mutation
• molecular docking
• molecular dynamics (MD) simulation
• immunoinformatics

Author contributions

CT, CL, and AW did the conceptualization. CT and JZ conducted data collection and analysis. CT wrote the manuscript. CT and JZ draw the figure. CL and AW reviewed and edited the article. CL and AW acquired the funding. All authors have read and agreed to the published version of the article.

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material; The Supplementary data was uploaded to Google Drive, available at: https://drive.google.com/file/d/1F7rytbCq8vaNiId75tSb23g6Aek2lKwJ/view?usp=drive_link.

Geolocation information

Changsha, Hunan province of China.

Table 1. List of mutational sites of different MPXV lineages.

Additional information

Funding

This work was supported by the National Key Research and Development Program of China [No. 2022YFC2009801; No. 2022YFC2009805], the Natural Science Foundation of Hunan Province [No. 2021JJ31071], the Project program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital)[No. 2021KFJJ05], Health Development Research Center of the National Health Commission, “Evidence-based Evaluation and Demonstration Base Construction Project of Infection Control Measures in Healthcare Institutions”[No. CNHDRC-KJ-L-2020-53-04375], and Scientific and technological personnel lifting Project in Hunan Province [No. 2023TJ-Z11].