Computational Prediction of <i>Plasmodium falciparum</i> Antigen-T-cell Receptor Interactions via Molecular Docking: Implications for Malaria Vaccine Design

Abstract Malaria is one of the deadliest diseases in sub-Saharan Africa and Southeast Asia. The majority of the fatalities occur mostly in children under 5 years and pregnant women and this is due to infection by Plasmodium spp, of which Plasmodium falciparum is the most virulent and is responsible for most of the morbidity and mortality. Despite various public health interventions such as use of insecticide-treated bed nets, spraying of homes with insecticides and use of WHO recommended artemisinin-based combination therapies (ACT), malaria prevention still faces major setback due to drug and insecticide resistance by P. falciparum and mosquitoes respectively. The study uses molecular docking and immunoinformatics to screen various Plasmodium spp antigens and evaluate their antigenicity and suitability as vaccine candidates. The P. falciparum antigens and T-cell receptor (TCR) structures were obtained from Protein Data Bank (PDB) based on a range of factors related to their role in the lifecycle of the parasite and their status as vaccine targets. Protein structures not available in the PDB were predicted using AlphaFold. The 3D structures of selected P. falciparum antigens and TCR structures were downloaded in PDB format then all water molecules, Hetatm, and bound ligands were deleted from the protein structures using BIOVIA Discovery Studio Visualizer. Subsequently, molecular docking was done using ClusPro v2.0 server and docked complexes were compared. The findings of this study gave valuable insights into the interaction of human immune response with P. falciparum antigens. The best three ranked antigen complexes are PfCyRPA, PfMSP10 and PfCSP and this confirm their use as potential candidates for vaccine development. This study highlights the usefulness of computational docking in identifying P. falciparum antigens of excellent immunogenic potential as vaccine candidates.