An immunoinformatics approach to promiscuous peptide design for the: Plasmodium falciparum erythrocyte membrane protein-1

Abstract

Plasmodium falciparum erythrocyte membrane protein-1 (Pfemp-1), a variant adhesion molecule, can act as a key component of immunity against malaria. In the current selection of malaria vaccines, no efficient vaccines are available that can be employed for its proper treatment. Unfortunately, resistance to post-infection treatments is increasing and therefore there is a pressing need to develop an efficient vaccine. Peptide-based vaccines can be effective tools against malaria but HLA restriction is a major hindrance which can be conquered by using promiscuous peptides. In this work, we employed a combined in silico and experimental approach to identify promiscuous peptides for the treatment of malaria. At first, using the immunoinformatics approach, promiscuous peptides were predicted from two conserved domains, CIDR-1 and DBL-3γ, of the Pfemp-1 antigen. These peptides were selected on the basis of their predicted binding affinity with different HLA class-I & class-II alleles. A total of 13 peptides were selected based on their predicted IFN-γ and IL-4 induction ability as well as their hydrophobicity. Out of these 13, the peptide C6 was synthesised and experimentally evaluated for further rationalization, HLA-peptide complex modelling and binding interaction analysis. Interestingly, the peptide C6 (SFIHIYLYRNIRIQL) showed an encouraging immunological response and T-cell proliferation in the immunological assay. This valuable content can aid the better design of more potent and selective vaccine candidates against infectious diseases.