Immunoinformatics-Based Designing of a Multi-Epitope Chimeric Vaccine From Multi-Domain Outer Surface Antigens of Leptospira.

Pankaj Kumar,Surabhi Lata,Umate Nachiket Shankar,Mohd Akif

doi:10.3389/fimmu.2021.735373

Abstract

Accurate information on antigenic epitopes within a multi-domain antigen would provide insights into vaccine design and immunotherapy. The multi-domain outer surface Leptospira immunoglobulin-like (Lig) proteins LigA and LigB, consisting of 12–13 homologous bacterial Ig (Big)-like domains, are potential antigens of Leptospira interrogans. Currently, no effective vaccine is available against pathogenic Leptospira. Both the humoral immunity and cell-mediated immunity of the host play critical roles in defending against Leptospira infection. Here, we used immunoinformatics approaches to evaluate antigenic B-cell lymphocyte (BCL) and cytotoxic T-lymphocyte (CTL) epitopes from Lig proteins. Based on certain crucial parameters, potential epitopes that can stimulate both types of adaptive immune responses were selected to design a chimeric vaccine construct. Additionally, an adjuvant, the mycobacterial heparin-binding hemagglutinin adhesin (HBHA), was incorporated into the final multi-epitope vaccine construct with a suitable linker. The final construct was further scored for its antigenicity, allergenicity, and physicochemical parameters. A three-dimensional (3D) modeled construct of the vaccine was implied to interact with Toll-like receptor 4 (TLR4) using molecular docking. The stability of the vaccine construct with TLR4 was predicted with molecular dynamics simulation. Our results demonstrate the application of immunoinformatics and structure biology strategies to develop an epitope-specific chimeric vaccine from multi-domain proteins. The current findings will be useful for future experimental validation to ratify the immunogenicity of the chimera.

Highlights

Leptospirosis is categorized as an emerging and neglected tropical zoonotic disease worldwide
Since the first six and half domains are conserved among the LigA and LigB proteins, the sequences corresponding to all 12 Ig-like domains from constant and variable regions of LigB were considered for the analysis, while the sequences corresponding to only variable Ig-like domains of LigA were used for antigenic epitope identification
Obtaining accurate knowledge of antigenic epitopes from several big or multi-domain proteins has been a laborious task due to constraints associated with the lack of high expression and purification and the subsequent structural studies

Summary

Introduction

Leptospirosis is categorized as an emerging and neglected tropical zoonotic disease worldwide. It is considered a public health problem globally, with an estimated 1 million leptospirosis cases reported each year, causing deaths of around 60,000 [1,2,3]. The infection usually shows symptoms such as headache, chills, illness, and muscle aches, and a more severe form of disease is associated with. Designing of a Multi-Epitope Chimeric Lig Vaccine multi-organ failure known as Weil’s disease. The causative agent, pathogenic Leptospira spp., includes more than 270 antigenically diverse serovars [4]. There is a lack of proper therapeutics and effective vaccines against pathogenic Leptospira. An advance in the development of new therapeutics and effective subunit vaccines is warranted

Results

Discussion

Conclusion