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.

Predicting Multi-Epitope Peptide Cancer Vaccine from Novel TAA Topo48

“…Following which, time and cost consuming addressed to conventional experiment also can be reduced by this method [32]. Moreover, vaccines designed by using in silico approaches have been tested over to clinical trials [33].…”

Computational design of immunogenic peptide constructs comprising multiple human leukocyte antigen restricted dengue virus envelope epitopes

“…Molecular docking studies and population coverage analysis provide further insight into the HLA‐promiscuity of the identified peptides. Many studies have employed CABS‐dock 26,73 for estimating HLA‐peptide interaction efficacy. Therefore, in this study, CABS dock was employed for estimation of RMSD values.…”

Novel Strategies for Malaria Vaccine Design

“…In a recent study, both in-silico and experimental approaches were used to identify antigenic epitopes from CIDR-1 and DBL-3γ conserved domains of PfEMP1. These epitopes were predicted to have good binding affinity to HLA molecules as well as the capability to induce IFN-γ, IL-4 secretion and T cell proliferation in exposed individuals ( 93 ).…”