Genome-wide identification of novel vaccine candidates for Plasmodium falciparum malaria using integrative bioinformatics approaches

Abstract

In spite of decades of malaria research and clinical trials, a fully effective and long-lasting preventive vaccine remains elusive. In the present study, 5370 proteins of Plasmodium falciparum genome were screened for the presence of signal peptide/anchor and GPI anchor motifs. Out of 45 screened surface-associated proteins, 22 were consensually predicted as antigens and had no orthologs in human and mouse except circumsporozoite protein (PF3D7_0304600). Among 22 proteins, 19 were identified as new antigens. In the next step, a total of 4944 peptides were predicted as CD8+ T cell epitopes from 22 probable antigens. Of these, the highest scoring 262 epitopes from each antigen were taken for optimization study in the malaria-endemic regions which covered a broad human population (~93.95%). The predicted epitope 13ILFYFFLWV21 of antigen 6-cysteine (PF3D7_1346800) was binding to the HLA-A*0201 allele with the highest fraction (26%) of immunogenicity in the target populations of North-East Asia, South-East Asia, and sub-Saharan Africa. Therefore, these epitopes are proposed to be favored in vaccine designs against malaria.