Antigen identification is an important step in the vaccine development process. Computational approaches including deep learning systems can play an important role in the identification of vaccine targets using genomic and proteomic information. Here, we present a new computational system to discover and analyse novel vaccine targets leading to the design of a multi-epitope subunit vaccine candidate. The system incorporates reverse vaccinology and immuno-informatics tools to screen genomic and proteomic datasets of several pathogens such as Trypanosoma cruzi, Plasmodium falciparum, and Vibrio cholerae to identify potential vaccine candidates (PVC). Further, as a case study, we performed a detailed analysis of the genomic and proteomic dataset of T. cruzi (CL Brenner and Y strain) to shortlist eight proteins as possible vaccine antigen candidates using properties such as secretory/surface-exposed nature, low transmembrane helix (< 2), essentiality, virulence, antigenic, and non-homology with host/gut flora proteins. Subsequently, highly antigenic and immunogenic MHC class I, MHC class II and B cell epitopes were extracted from top-ranking vaccine targets. The designed vaccine construct containing 24 epitopes, 3 adjuvants, and 4 linkers was analysed for its physicochemical properties using different tools, including docking analysis. Immunological simulation studies suggested significant levels of T-helper, T-cytotoxic cells, and IgG1 will be elicited upon administration of such a putative multi-epitope vaccine construct. The vaccine construct is predicted to be soluble, stable, non-allergenic, non-toxic, and to offer cross-protection against related Trypanosoma species and strains. Further, studies are required to validate safety and immunogenicity of the vaccine.

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BackgroundThe trehalose metabolic enzymes have been considered as potential targets for drug or vaccine in several organisms such as Mycobacterium, plant nematodes, insects and fungi due to crucial role of sugar trehalose in embryogenesis, glucose uptake and protection from stress. Trehalose-6-phosphate phosphatase (TPP) is one of the enzymes of trehalose biosynthesis that has not been reported in mammals. Silencing of tpp gene in Caenorhabditis elegans revealed an indispensable functional role of TPP in nematodes.Methodology and Principal FindingsIn the present study, functional role of B. malayi tpp gene was investigated by siRNA mediated silencing which further validated this enzyme to be a putative antifilarial drug target. The silencing of tpp gene in adult female B. malayi brought about severe phenotypic deformities in the intrauterine stages such as distortion and embryonic development arrest. The motility of the parasites was significantly reduced and the microfilarial production as well as their in vitro release from the female worms was also drastically abridged. A majority of the microfilariae released in to the culture medium were found dead. B. malayi infective larvae which underwent tpp gene silencing showed 84.9% reduced adult worm establishment after inoculation into the peritoneal cavity of naïve jirds.Conclusions/SignificanceThe present findings suggest that B. malayi TPP plays an important role in the female worm embryogenesis, infectivity of the larvae and parasite viability. TPP enzyme of B. malayi therefore has the potential to be exploited as an antifilarial drug target.

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