Abstract Description

The endemic areas are facing the highest burden of malaria associated with the evolution of resistance emerging from the pharmacology of antimalarial drugs. This has advanced to rendering the effectiveness of antimalarial agents inconsequential. Therefore, a new generation of more effective and multi targeting vaccine against malaria is mandatory. This study explored bioinformatics and immunoinformatics approaches to construct a potential multi-epitope-based vaccine that could potentially prevent the malaria blood stage. Four protein sequences of malaria Plasmodium falciparum were retrieved from the protein data bank (PDB). The Bepipred linear epitope prediction 2.0 online server was used to Predicted B-cell epitopes and the IEDB server was used to predict HTL and CTL epitopes. Additionally, to validate the toxicity, allergenicity, antigenicity and physicochemical parameters of the construct vaccine were performed using online servers. The three stable linkers, such as KK, AAY, GPGPG were used to link the selected epitopes for vaccine construction and the selected adjuvant was linker on the N-terminal of the construct using EAAK linker. Subsequently, the molecular docking and simulation studies were conducted to evaluate possible interactions between the vaccine construct and the toll-like receptor (TLR8). Furthermore, immune simulation and codon adaptation were conducted. The designed vaccine construct was predicted to be antigen, non-toxic and non-allergen. Furthermore, the physicochemical parameters predicted that the construct was stable, thus essential for in vitro protein expression with grand average hydropathicity of -0.311. The docking results showed that the designed vaccine could potentially induce innate immunity by interaction with TLR8 and a binding energy of -21.7 kcal/mol. Furthermore, molecular dynamics simulation confirmed this statement as bound TLR8 had higher RMSD value fluctuation than unbound TLR8, confirming conformational changes in the receptor. Immunity simulation of the designed vaccine reported B-cell proliferation, generation of memory B-cell, production of the helper and cytotoxic T-cell immune response and increased IFN-γ. In conclusion, the designed multi-epitope-based vaccine could potentially be a candidate against P. falciparum blood stage. However, the most essential studies; in vivo and in vitro; are highly recommended.