IN SILICO APPROACH FOR FUTURE DEVELOPMENT OF SUBUNIT VACCINES AGAINST LEPTOSPIRA INTERROGANS SEROVAR LAI

Abstract

Leptospirosis continues to have major impacts on people of developing countries with inestimable morbidity and mortality. As current leptospirosis vaccination is relatively unsuccessful, development of efficacious vaccines through novel means became utmost priority for prevention of frequent outbreaks of the disease. Herein, MHC class II restricted peptide epitopes were identified from pathogenic leptospiral membrane proteins to suggest T-cell epitope driven leptospirosis vaccines through reverse vaccinology. The proteome of Leptospira interrogans serovar Lai was screened to select 137 membrane proteins. Jemboss Antigenic server was employed to find antigenic peptides, followed by ProPred analysis to predict 30 short peptides having strong binding affinity with HLA DRB1*0101, DRB1*0401 and DRB1*1501 alleles. Predictions were revised to pick antigenic peptides with same core region binding with the selected HLA- DRB1 alleles and ten such peptides were found from seven proteins. Further, to confirm the interaction at structure level, Leptospira excinuclease ABC subunit B protein having short T-cell antigenic peptide (133- REDVVIVSSVSCIYGLG-149) was modeled using Modeller9v7. The model reliability was evaluated through Procheck, ProSA and ProQ. Docking calculations for selected HLA DRB1 alleles (receptor) and modeled Leptospira excinuclease ABC subunit B protein (ligand) were carried out using Hex 5.1. The protein -protein interaction revealed that the core region (136-VVIVSSVSC-144) of the antigenic peptide (133- REDVVIVSSVSCIYGLG-149) was well interacting with the receptors. Through the reverse vaccinology approach and docking studies, the short antigenic peptide 133-REDVVIVSSVSCIYGLG-149 of Leptospira excinuclease ABC subunit B is proposed as a potential novel T-cell driven subunit vaccine against leptospirosis.