IMMUNOINFORMATICS-AIDED DESIGN OF A MULTI-EPITOPE VACCINE AGAINST MPOX

Abstract

Mpox, previously called monkeypox is zoonotic disease caused by the Monkeypox virus. Recent global outbreaks in non-endemic countries demonstrated its significance as a threat to public health. Currently, there are no preventive therapies or vaccines which target Mpox specifically. Herein, we aim to identify immunodominant B and T cell epitopes from this virus and design subunit vaccines using a reverse vaccinology approach. Four target proteins, H3L, M1R, B6R and A35R which have crucial functions in the pathogenesis of this virus were selected for epitope mapping. Epitopes with high population coverage and promiscuity were shortlisted and fused with appropriate adjuvants and linkers. Four vaccine constructs were designed using epitopes from a single protein and one vaccine was formed using epitopes from the proteins in combination. All constructs were predicted to be antigenic and non-allergenic with suitable physicochemical parameters. The three-dimensional structure of all constructs was predicted via homology modelling. Molecular docking analysis revealed stable and energetically favourable interactions between cytotoxic T lymphocyte (CTL) epitopes and human leukocyte antigen (HLA) alleles and between vaccine constructs and toll-like receptors (TLRs) (2, 3 and 4). These results obtained show that the MPXV multi-epitope vaccines (MEVs) have a strong binding affinity to human immune receptors, although extensive experimental testing is required to show that the predicted strong binding with human immune receptors translates to robust immune responses against MPXV in situ.