In silico design and immunoinformatics analysis of a universal multi-epitope vaccine against monkeypox virus

Abstract

Monkeypox virus (MPXV) outbreaks have been reported in various countries worldwide; however, there is no specific vaccine against MPXV. In this study, therefore, we employed computational approaches to design a multi-epitope vaccine against MPXV. Initially, cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), linear B lymphocytes (LBL) epitopes were predicted from the cell surface-binding protein and envelope protein A28 homolog, both of which play essential roles in MPXV pathogenesis. All of the predicted epitopes were evaluated using key parameters. A total of 7 CTL, 4 HTL, and 5 LBL epitopes were chosen and combined with appropriate linkers and adjuvant to construct a multi-epitope vaccine. The CTL and HTL epitopes of the vaccine construct cover 95.57% of the worldwide population. The designed vaccine construct was found to be highly antigenic, non-allergenic, soluble, and to have acceptable physicochemical properties. The 3D structure of the vaccine and its potential interaction with Toll-Like receptor-4 (TLR4) were predicted. Molecular dynamics (MD) simulation confirmed the vaccine’s high stability in complex with TLR4. Finally, codon adaptation and in silico cloning confirmed the high expression rate of the vaccine constructs in strain K12 of Escherichia coli (E. coli). These findings are very encouraging; however, in vitro and animal studies are needed to ensure the potency and safety of this vaccine candidate.

In-silico formulation of a next-generation polyvalent vaccine against multiple strains of monkeypox virus and other related poxviruses

“…Additionally, investigating the molecular interactions between the vaccine and TLRs holds important implications for future research on preventing and managing infections or pandemics caused by monkeypox virus and related viruses. In silico epitope based vaccine were previously studied for different pathogenic organisms [63][64][65][66][67][68]. Two virulent proteins of monkeypox virus MPXVgp165 and Virion core protein P4a, were selected based on their similarity between targeted species, stability, and antigenicity.…”

Designing of a multi-epitopes based vaccine against Haemophilius parainfluenzae and its validation through integrated computational approaches

“…The significance of BamA lies in its contribution to the structural integrity and functionality of the outer membrane, making it a crucial component for various cellular activities across different biological systems ( 104 ). The identification of CTL (Cytotoxic T Lymphocyte), HTL (Helper T Lymphocyte), and linear B-cell epitopes in our study adhered to stringent criteria ( 105 ). It takes B-cell epitopes to trigger humoral immune responses, leading to the neutralization of pathogenic agents and the establishment of a memory response for future encounters ( 106 ).…”

“…Interestingly, the selected epitopes covered around 90% of the world’s population combined. We used overlapping lead MHC-I, MHC-II, and B-cell epitopes to develop multi-epitope-based chimeric vaccine constructs, incorporating particular linker and adjuvant sequences for increased efficacy ( 105 ). Similar in-silico techniques have been effectively used to create vaccine constructions that protect against a variety of diseases ( 70 ).…”

Immunized mice naturally process in silico-derived peptides from the nucleocapsid of SARS-CoV-2

“…Several computational approaches as predictive algorithms of epitopes have been used to design multi-epitope vaccines, such as cytotoxic T lymphocyte, helper T lymphocyte, and linear B lymphocyte epitopes [ 27 , 28 ]. Thus, bioinformatic tools can be used to evaluate the peptides’ allergenicity and toxicity, as well as their ability to induce IFN-γ production (helper T lymphocytes) [ 27 , 29 ].…”