Immunoinformatics design of multivalent epitope vaccine against monkeypox virus and its variants using membrane-bound, enveloped, and extracellular proteins as targets

Abstract

IntroductionThe current monkeypox (MPX) outbreak, caused by the monkeypox virus (MPXV), has turned into a global concern, with over 59,000 infection cases and 23 deaths worldwide.ObjectivesHerein, we aimed to exploit robust immunoinformatics approach, targeting membrane-bound, enveloped, and extracellular proteins of MPXV to formulate a chimeric antigen. Such a strategy could similarly be applied for identifying immunodominant epitopes and designing multi-epitope vaccine ensembles in other pathogens responsible for chronic pathologies that are difficult to intervene against.MethodsA reverse vaccinology pipeline was used to select 11 potential vaccine candidates, which were screened and mapped to predict immunodominant B-cell and T-cell epitopes. The finalized epitopes were merged with the aid of suitable linkers, an adjuvant (Resuscitation-promoting factor), a PADRE sequence (13 aa), and an HIV TAT sequence (11 aa) to formulate a multivalent epitope vaccine. Bioinformatics tools were employed to carry out codon adaptation and computational cloning. The tertiary structure of the chimeric vaccine construct was modeled via I-TASSER, and its interaction with Toll-like receptor 4 (TLR4) was evaluated using molecular docking and molecular dynamics simulation. C-ImmSim server was implemented to examine the immune response against the designed multi-epitope antigen.Results and discussionThe designed chimeric vaccine construct included 21 immunodominant epitopes (six B-cell, eight cytotoxic T lymphocyte, and seven helper T-lymphocyte) and is predicted non-allergen, antigenic, soluble, with suitable physicochemical features, that can promote cross-protection among the MPXV strains. The selected epitopes indicated a wide global population coverage (93.62%). Most finalized epitopes have 70%–100% sequence similarity with the experimentally validated immune epitopes of the vaccinia virus, which can be helpful in the speedy progression of vaccine design. Lastly, molecular docking and molecular dynamics simulation computed stable and energetically favourable interaction between the putative antigen and TLR4.ConclusionOur results show that the multi-epitope vaccine might elicit cellular and humoral immune responses and could be a potential vaccine candidate against the MPXV infection. Further experimental testing of the proposed vaccine is warranted to validate its safety and efficacy profile.

Deciphering the Immunogenicity of Monkeypox Proteins for Designing the Potential mRNA Vaccine

“…Although some other studies also focused on designing an immunoinformatics-based vaccine against MPXV, the proteins utilized in these studies are different from the protein used in this study. ,, In a similar study, the EEV Type-I membrane glycoprotein was used, but the predicted epitopes are different to those predicted in this study . Similarly, another study predicted the epitope “FSIGGVIHL” and used it for the formulation of the vaccine against MPXV; however, our designed vaccine binds more strongly with the human toll-like receptors as compared to the vaccine designed in that study .…”

“…68,90,91 In a similar study, the EEV Type-I membrane glycoprotein was used, but the predicted epitopes are different to those predicted in this study. 91 Similarly, another study predicted the epitope "FSIGGVIHL" and used it for the formulation of the vaccine against MPXV; however, our designed vaccine binds more strongly with the human toll-like receptors as compared to the vaccine designed in that study. 68 Furthermore, the vaccine designed in this study is effective for individuals worldwide because the epitopes of vaccine covered 100% of the world population.…”

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

“…Waqas et al . (2023) assembled the best B- and T-cell epitopes obtained from A35R, A43R, B16R, B21R, C4L, E8L, E13L, E21R, and G10R proteins into a vaccine construct and used RpfE sequence as an adjuvant to boost vaccine immunogenicity [ 102 ]. In the study by Zaib et al .…”

“…According to population coverage analysis, the vaccine construct covers 95.57% of the worldwide population, while the vaccine designed in study of Waqas et al . covers 93.62% of the worldwide population [ 102 ]. The high antigenicity scores predicted by the VaxiJen 2.0 server and the ANTIGENpro server showed that the proposed vaccine is effective enough to elicit strong immune responses in the body.…”

Relapse of inflammatory skin diseases following vaccination against monkeypox

“…12 In this immunologic environment, the further possibility that the multi-epitope vaccines can trigger an exacerbation of inflammatory skin disease in genetically predisposed patients. 13 Interestingly, the relapse of autoimmune conditions as psoriasis and AD could be related to the aberrant activation of the Tissueresident memory (TRM) T cells, a newly identified subset of memory T cells originating from the differentiation of naive T cells in the skin following antigen exposure. TRM cells persist long-term in tissues without recirculating in the blood thus providing a first line of adaptive cellular defense.…”