In silico prediction of vaccine candidate b cell epitopes of plasmodium falciparum circumsporozoite protein for the control of malaria

Abstract

Malaria remains one of the most infectious diseases worldwide causing an estimate of 249 million cases and 608,000 deaths annually predominantly among children under five years of age. Malaria is caused by plasmodium parasites with Plasmodium falciparum (pf), being the deadliest human malaria parasite. Sporozoites, the infective stage of malaria parasite, develop in mosquitoes and are inoculated into the mammalian host through infected mosquito bites where they ultimately must go to the liver, invade hepatocytes and develop into exoerythrocytic stage. Key to the parasite's lifecycle is the circumsporozoite protein (CSP), a sporozoite’s major surface protein required for sporozoites development and facilitates the journey of Plasmodium sporozoites from the mosquito midgut to the mammalian liver. The emergence of partial artemisinin resistance in Africa and recent reports in Uganda underscore the ongoing challenges in malaria control efforts, prompting heightened concern and need for a highly effective vaccine particularly against Plasmodium falciparum. In-silico analysis of pfcsp protein was carried out in order to identify epitopes that can be used in anti-malarial vaccine development. Motif analysis was carried out to identify peptide motifs. Chou and Fasman Beta-Turn, Karplus and Schulz Flexibility, BepiPred linearity, Kolaskar antigenicity and Parker Hydrophilicity prediction tools were used to predict these motifs’ potential to induce B-cell mediated immune responses. Out of the ten peptide motifs, one motif was identified as a potential epitope and this was motif 62-67 because it passed the linearity, surface accessibility and antigenicity tools. The motif was mapped on the structure of the circumsporozoite protein (CSP) and this was extracellular. This motif can be used in the development of anti-malarial vaccine. Further analyses such as molecular biology and in vivo immunization assays are required to validate these findings.