Multiepitope‐based vaccine design by exploring antigenic potential among leptospiral lipoproteins using comprehensive immunoinformatics and structure‐based approaches

Abstract

Leptospirosis is a tropical and globally neglected zoonotic disease caused by pathogenic spirochetes, Leptospira. Although the disease has been studied for decades, a potent or effective vaccine is not available so far. Efforts are being made to design an efficient vaccine candidate using different approaches. Immunoinformatics approaches have been proven to be promising in terms of time and cost.Here, we used immunoinformatics and structure-based approaches to evaluate antigenic B-and T-cell epitopes present on the leptospiral lipoproteins (LipL).The promiscuous overlapping epitopes (B-cell, T-cell, interferon (IFN)-γ positive, and non-allergens), which can induce humoral, cell-mediated, and innate immunity, were selected to generate a multiepitope chimeric vaccine. To enhance the vaccine immunogenicity, a Toll-like receptor (TLR) agonist was fused to the vaccine with a suitable linker. The chimeric vaccine structure was predicted for molecular docking studies with immune receptors. Moreover, the stability of the vaccine-immune receptor complexes was analyzed by normal mode analysis (NMA). The potency of the vaccine construct was predicted by the immune simulation tool. The study provides additional information toward constructing peptide-based chimeric vaccines against Leptospira.

A New Recombinant Multiepitope Chimeric Protein of Leptospira interrogans Is a Promising Marker for the Serodiagnosis of Leptospirosis

“…chimeric constructions have been designed and explored for vaccine [34][35][36][37], but their potential as a diagnostic marker has not been explored yet. Other published dry lab studies explored possible new chimeric construction by using a combination of epitope prediction and molecular docking for vaccine and/or diagnostic goals [38,39].…”

Enhancement of clinical signs in C3H/HeJ mice vaccinated with a highly immunogenicLeptospiramethyl-accepting chemotaxis protein following challenge

“…Continuous improvements in bioinformatics tools provide the opportunity to identify proteins based on their potential structures, biological function, and capacity to induce protective humoral and cellular immune responses (23)(24)(25). The in-silico prediction of potential immunogenic Leptospira proteins can be used to effectively identify target molecules that can generate both humoral and/or cell mediated immune responses (26)(27)(28)(29). In addition, studies have focused on the discovery of new vaccine candidates based on immune responses elicited by interactions of the ORFome of L. interrogans through microarrays (30), reverse and structural vaccinology and/or cell-surface immunoprecipitation (22,23,31), and the immunization with live avirulent/attenuated vaccines (32)(33)(34)(35).…”