# Annotation of the Extracellular Enveloped Form of Monkeypox Virus for the Design, Screening, Validation, and Simulation of a Chimeric Vaccine Construct

## TL;DR

This study designs a potential monkeypox vaccine using computational methods to target the virus's outer form and predict immune response.

## Contribution

A novel multi-epitope vaccine candidate (MPXV-1-Beta) is proposed for monkeypox with strong predicted immune activation and global population coverage.

## Key findings

- MPXV-1-Beta showed high antigenicity, solubility, and structural stability in simulations.
- The vaccine candidate demonstrated stable interactions with TLR2, TLR4, and MHC molecules.
- It is predicted to trigger immune responses in over 97% of the global population.

## Abstract

The human monkeypox virus (hMPXV) is a recently growing public health concern, prompting the necessity for effective vaccines. In this study, reverse vaccinology was leveraged to design a multi-epitope vaccine formulation (MPXV-1-Beta) targeting the extracellular enveloped virus (EEV). The safety, efficacy, and capability of the MPXV-1-Beta vaccine to trigger strong immune responses was assessed. The MPXV-1-Beta exhibited high antigenicity, good solubility, and structural reliability. When assessed through docking and simulations, it reflected stable interactions with TLR2, TLR4, and MHC molecules, suggesting its ability to elicit an immune response effectively with over 97% of global population coverage. These results highlight MPXV-1-Beta as a potential vaccine formulation against hMPXV. However, further laboratory and clinical validation is needed.

Recent outbreaks caused by hMPXV, especially hMPXV lineages/sub-lineages, represent public health threats necessitating stringent prophylactic measures to ameliorate their colossal impact. The current study annotated the EEV form of hMPXV’s target proteins to formulate a reverse vaccinology-dependent hMPXV multiepitope vaccine. Epitope determination, followed by vaccine formulation, was undertaken. The promising formulation was validated for its potential to trigger immune responses immunoinformatically. The MPXV-1-Beta formulation was characterised as a promising candidate based on antigenicity score, physicochemical properties, solubility score, ProSA Z-score, and Ramachandran plot. Docking, normal mode analysis, and molecular dynamic simulation of MPXV-1-Beta with TLRs and MHCs authenticated rigid docking and its efficacy in enhancing immune receptor activation under physiological conditions. MPXV-1-Beta was discerned to trigger a sustained immune response (IR) with a broader average population coverage of 97.526, SD = 12.44. The proposed MPXV-1-Beta candidate showed significant potential. The findings of this study provide a preliminary framework for developing an efficacious hMPXV vaccine; however, extensive in vitro, in vivo, and clinical evaluations are required to substantiate the computational insights.