Immuno-informatics based approaches to design a novel multi epitope-based vaccine for immune response reinforcement against Leptospirosis

摘要

Leptospirosis is known as a zoonotic disease of global importance originated from infection with the spirochete bacterium Leptospira. Although several leptospirosis vaccines have been tested, the vaccination is-relatively unsuccessful in clinical application despite decades of research. Therefore, this study was conducted to construct a novel multi-epitope based vaccine against leptospirosis by using Hapl, LigA, LAg42, SphH and HSP58 antigens. T cell and IFN gamma epitopes were predicted from these antigens. In addition, to induce strong CD4 helper T lymphocytes (HTLs) responses, Pan HLA DR-binding epitope (PADRE) and helper epitopes selected from Tetanus toxin fragment C (TITrC) were applied. Moreover, for boosting immune response, Heparin-Binding Hemagglutinin (HBHA), a novel TLR4 agonist was added to the construct as an adjuvant. Finally, selected epitopes were linked together using EAAAK, GPGPG, AAY and HEYGAEALERAG linkers. Based on the predicted epitopes, a multi-epitope vaccine was construct with 490 amino acids. Physico-chemical properties, secondary and tertiary structures, stability, intrinsic protein disorder, solubility, and allergenicity of this vaccine construct were assessed by applying immunoinformatics analyses. A soluble, and non-allergic protein with a molecular weight of 53.476 kDa was obtained. Further analyses validated the stability of the chimeric protein and the predicted epitopes in the chimeric vaccine indicated strong potential to induce B-cell and T-cell mediated immune response. Therefore, immunoinformatics analysis showed that the modeled multi-epitope vaccine can properly stimulate the both T and B cells immune responses and could potentially be used for prophylactic or therapeutic usages.