Exploring dengue genome to construct a multi-epitope based subunit vaccine by utilizing immunoinformatics approach to battle against dengue infection

Abstract

Dengue is considered as a major health issue which causes a number of deaths worldwide each year; tropical countries are majorly affected by dengue outbreaks. It is considered as life threatening issue because, since many decades not a single effective approach for treatment and prevention of dengue has been developed. Therefore, to find new preventive measure, we used immunoinformatics approaches to develop a multi-epitope based subunit vaccine for dengue which can generate various immune responses inside the host. Different B-cell, TC cell, and TH cell binding epitopes were predicted for structural and non-structural proteins of dengue virus. Final vaccine constructs consisting of TC and TH cell epitopes and an adjuvant (β-defensin) at N-terminal of the construct. Presence of B-cell and IFN-γ inducing epitopes confirms the humoral and cell mediated immune response developed by designed vaccine. Designed vaccine was not found allergic and was potentially antigenic in nature. Modeling of tertiary structure and the refined model was used for molecular docking with TLR-3 (immune receptor). Molecular docking and dynamics simulation confirms the microscopic interactions between ligand and receptor. In silico cloning approach was used to ensure the expression and translation efficiency of vaccine within an expression vector.

Structural Basis and Designing of Peptide Vaccine using PE-PGRS Family Protein of Mycobacterium ulcerans – An Integrated Vaccinomics Approach

“…Furthermore, the vaccine-TLR2 complex was found to be stable during MD simulation where protein backbone undergone some microscale-changes (⁓7.67 Å) and mild fluctuations in their side-chain residues that can occur due to the flexible regions Pandey, Bhatt, and Prajapati 2018). These results are in line with the previous study where stabilization of vaccinereceptor complex was achieved within similar time-scale (M. Ali et al 2017;Mirza et al 2016). The hydrogen bond helps in molecular recognition by providing specificity and directionality to the interaction (Hubbard and Kamran Haider 2010).…”

Towards the first multi-epitope recombinant vaccine against Crimean-Congo hemorrhagic fever virus: A computer-aided vaccine design approach

“…Quality of the refined model was assigned by Ramachandran plot, ERRAT quality factor, and ProSA z-score, and the results demonstrated that the quality of the refined model was significantly improved. Since discontinuous B-cell epitopes as well as IFN-γ inducing epitopes have a crucial role in humoral and cell-mediated adaptive immune responses by producing antibodies and stimulating macrophages and natural killer cells, prediction of the epitopes currently are highly considered for vaccine design [13]. Subsequently, prediction of discontinuous B-cell epitopes and IFN-γ inducing epitopes were performed.…”

“…Furthermore, there are some drawbacks associated with conventional vaccines including weak immunity, multi-dose administration, allergenic potential and low safety. Consequently currently, new vaccine platforms such as Subunit Vaccines, DNA vaccine, and multi-epitope vaccine (MEV) are highly regarded [13]. Among them, due to high specificity, safety and low-cost production of MEVs these vaccines have attracted attention.…”

Positive selection pressure on E2 protein of classical swine fever virus drives variations in virulence, pathogenesis and antigenicity: Implication for epidemiological surveillance in endemic areas

“…The main objective of the immunoinformatics is to convert and organize large‐scale immunological data combining statistical and machine learning systems, to obtain immunologically meaningful interpretations (Soria‐Guerra, Nieto‐Gomez, Govea‐Alonso, & Rosales‐Mendoza, ). The proper use of immunoinformatics tools has shown a high degree of accuracy; therefore, this discipline has been employed to characterize molecular interactions between epitopes defining new hypotheses related to understand the immune system mechanisms (Wang et al, ), as well as to develop new multi‐epitope vaccine strategies against emergent viral diseases such as Zika virus (Dikhit et al, ; Pradhan et al, ), and Ebola virus (Dikhit et al, ), or re‐emerging viruses: Hepatitis C virus (Ashraf, Bilal, Mahmood, Hussain, & Mehboob, ) and Dengue virus (Ali et al, ). In this study, we used immunoinformatics approach to characterize both T‐cell and B‐cell epitopes for the main immunogenic protein of CSFV (E2 protein).…”