Title : A multi-epitope vaccine designed through comparative proteomics and computational modeling against the carcinogenic liver fluke opisthorchis viverrini
Abstract:
Opisthorchis viverrini (Ov), a Southeast Asian liver fluke, thrives within bile ducts, evading host immune responses and promoting cholangiocarcinoma in humans in humans in humans in humans in humans . A tegument of O. viverrini parasite plays a crucial role in host-parasite interactions and sustaining its survival within the host biliary environment. Here we employ an integrated multi-omic approach combined with computational techniques to identify immunogenic proteins with vaccine potential against O. viverrini. Comparative proteomic profiling of resistant and susceptible host models unveiled paramyosin as predominantly expressed throughout developmental stages in resistant hosts, while its expression was notably lower in susceptible hosts.
Paramyosin facilitates muscle contraction and motility in the liver fluke parasite. Bioinformatic analysis identified B cell epitopes within membrane-exposed regions of paramyosin at myosin tail domain. Additional tools predicted MHC-binding epitopes inducing T-cell responses. The identification of conformational B-cell epitopes and cytokine-inducing epitopes confirms the activation of both humoral and cell-mediated immune responses triggered by the constructed vaccine model. Molecular docking showed vaccine interactions with Toll-like receptor 4 (TLR-4) to trigger innate immunity by strong binding affinity and hence putatively confirms its ability to elicit an immune response. The reverse translated vaccine sequence was virtually cloned in the PET28A(+) plasmid after the optimization of the gene sequence.
Furthermore, synthetic long peptides encoding paramyosin epitopes stimulated high antibody titers and IFN-γ secretion upon immunostimulation in silico, demonstrating immunogenicity. Overall, our study demonstrates the power of integrating multi-disciplinary omic data and computational design for developing interventions against prevalent parasites such as O. viverrini trematode. This integrated multi-faceted approach can accelerate the characterization of targets for parasitic diseases globally.
Key words: Opisthorchis viverrini, cholangiocarcinoma, opisthorchiasis, immunoproteomics, immunoinformatics, Multi-epitope vaccine
Audience Take Away:
- Blend of wet lab and In-silico: Use of integrated omics and computational approach in diverse hosts can effectively identify immunogenic vaccine candidate proteins against helminth parasites.
- Recombinant vaccine mimicking resistant hosts: Comparative immunoproteomics by use of resistant vs susceptible host models may reveal antigenic/immunogenic protein that can manipulated and used for vaccine.
- Computational tools for vaccine evaluation: Use of best available tools in predicting antigenic epitopes, MHC binding potential, prediction of structures, and docking in epitope-based vaccine design.
- Accelerating intervention development: Integrating various omics data with bioinformatics analyses represents a powerful strategy for accelerating intervention development against prevalent parasitic infections globally.
