Design of a multi-epitope subunit vaccine for immune-protection against Leishmania parasite

Abstract

Visceral Leishmaniasis (VL) is an insect-borne neglected disease caused by the protozoan parasite Leishmania donovani. In the absence of a commercial vaccine against VL, chemotherapy is currently the only option used for the treatment of VL. Vaccination has been considered as the most effective and powerful tool for complete eradication and control of infectious diseases. In this study, we aimed to design a peptide-based vaccine against L. donovani using immunobioinformatic tools. We identified 6 HTL, 18 CTL, and 25 B-cell epitopes from three hypothetical membrane proteins of L. donovani. All these epitopes were used to make a vaccine construct along with linkers. An adjuvant was also added at the N-terminal to enhance its immunogenicity. After that, we checked the quality of this vaccine construct and found that it is nontoxic, nonallergic, and thermally stable. A 3D structure of the vaccine construct was also generated by homology modeling to evaluate its interaction with innate immune receptors (TLR). Molecular docking was performed, which confirmed its binding with a toll-like receptor-2 (TLR-2). The stability of vaccine-TLR-2 complex and underlying interactions were evaluated using molecular dynamic simulation. Lastly, we carried out in silico cloning to check the expression of the final designed vaccine. The designed vaccine construct needs further experimental and clinical investigations to develop it as a safe and effective vaccine against VL infection.

Designing multiepitope-based vaccine against Eimeria from immune mapped protein 1 (IMP-1) antigen using immunoinformatic approach

“…They proved through vaccination of three-week-old AA broiler chickens that recombinant EtIMP1-flagellin fusion protein enhanced the immune response of chickens, making it an effective immunogen 15 . Molecular docking results were further validated using molecular dynamics simulation, where obtained RMSD, RMSF and energy decomposition analysis revealed significant interaction of the vaccine construct and the TLR5 51 , 54 .…”

“…The T-cell and B-cell epitope prediction is achieved through IEDB servers and ABCpred server, respectively. Several recent studies have implemented these tools to predict epitopes and develop multiepitope vaccines 17 , 34 , 36 , 51 , 59 . Even though most prediction tools used to identify B-cells have low accuracy, ABCpred has been considered one of the most effective epitope prediction servers available with an accuracy of 65.93% 26 .…”

“…Docked complex of MEV and TLR5 was further subjected to energy minimisation through molecular dynamics simulations (MDS) using AMBERS 14 package 50 . MDS was performed to evaluate complex stability and interactions between the docked proteins 51 . The input proteins were described using FF14SB 52 , and topologies of the vaccine structure were generated using the LEAP module of AMBER 14.…”

“…The JCat adaptation is dependent on the codon adaptation index (CAI) and percentage GC content of improved sequence. The optimal CAI score of optimised gene sequence ranges from is 0.8 to 1.0 and GC% (30–70%), indicating improved expression of a gene in its corresponding organism, without any translation errors 51 . The optimised nucleotide sequence of the vaccine was cloned and expressed in E. coli (strain K12) host, where XhoI (CTCGAG) and BamHI (GGATCC) restriction sites were added to 5` and 3` ends of the construct prior to cloning, respectively.…”

Integrated Core Proteomics, Subtractive Proteomics, and Immunoinformatics Investigation to Unveil a Potential Multi-Epitope Vaccine against Schistosomiasis

“…Immunoinformatics approaches are a viable option for developing and designing highly immunogenic MEVs. Immunoinformatics has recently been used to design MEVs against viruses [ 16 , 17 , 18 , 19 , 20 , 21 ], parasites [ 22 , 23 ], and bacteria [ 24 , 25 , 26 , 27 , 28 ].…”