In silico study to predict promiscuous T cell and B cell-epitopes derived from the vaccine candidate antigens of Plasmodium vivax binding to MHC class-II alleles
Nazam Khan1, Mona N Bin-Mwena1, Mashael W Alruways1, Noor Motair M Allehyani1, Maryam Owaid Alanzi1, Shahzad2, Amir Khan3, Rakesh Sehgal4, PK Tripathi4, Umar Farooq5
1 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Shaqra, Kingdom of Saudi Arabia
2 Universal Group of Institutions, Lalru, Punjab, India
3 Department of Basic Oral Medicine and Allied Dentistry, College of Dentistry, Taif University, Taif, Kingdom of Saudi Arabia
4 Postgraduate Institute of Medical Education and Research, Chandigarh, India
5 Department of Basic Oral Medicine and Allied Dentistry, College of Dentistry, Taif University, Taif, Kingdom of Saudi Arabia; Faculty of Biotechnology and Applied Sciences, Shoolini University, Solan, HP, India
Department of Basic Oral Medicine and Allied Dentistry, College of Dentistry, Taif University, Taif, KSA; Faculty of Biotechnology and Applied Sciences, Shoolini University, Solan, HP, India
Source of Support: None, Conflict of Interest: None
Malaria is still one of the major causes of health and disability globally, even after tremendous efforts to eradicate the parasite. Till date a highly effective vaccine is not available for its control. The primary reason for the low efficacy of vaccines is extensive polymorphism in potential vaccine candidate antigen genes and HLA polymorphisms in the human population. This problem can be resolved by developing a vaccine using promiscuous peptides to combine the number of HLA alleles.
This study predicted that T and B cell epitopes (Promiscuous peptides) by targeting PPPK-DHPS and DHFR-TS proteins of P. vivax, using different in silico tools. Selected peptides were characterised as promiscuous peptides on the basis of their immunogenicity, antigenicity and hydrophobicity. Furthermore, to confirm their immunogenicity, these peptides were utilized for molecular modelling and docking analysis.
For determining the requisite affinity with distinct HLA Class-I, and HLA Class-II alleles, only five peptides for DHFR-TS and 3 peptides for PPPK-DHPS were chosen as promiscuous peptides. The D1 peptide has the maximum binding energy with HLA alleles, according to HLA-peptide complex modelling, and binding interaction analyses. These findings could lead to the development of epitope-based vaccinations with improved safety and efficacy. These epitopes could be the major vaccine targets in P. vivax as they possess a higher number of promiscuous peptides. Also, the B cell epitopes possess maximum affinity towards different alleles as analysed by docking scores. However, further investigation is warranted using in vitro and in vivo models.