Effect of dietary supplementation with yeast cell wall extracts on performance and gut response in broiler chickens.

UNLABELLED: Hepatitis C Virus (HCV) is a significant global health threat that leads to chronic liver disease, cirrhosis, and hepatocellular carcinoma. While antiviral therapies have advanced over the years, they face challenges such as the high cost, drug resistance, and the absence of a prophylactic vaccine. This study focused on developing a new multi-epitope-based vaccine using in-silico methods targeting the conserved NS5B protein of HCV, known for its crucial role in viral replication. Identification and screening of B-cell and T-cell epitopes as highly antigenic, immunogenic, and non-allergenic were performed using immuno-informatics tools. The epitopes were conjugated with adjuvants and linkers (EAAAK, GPGPG, and AAY) to improve immunogenicity and stability. The physicochemical properties, antigenicity, and population coverage of the vaccine construct were evaluated. Molecular docking and dynamics simulations indicated stable and significant interactions with TLRs that ensured robust innate immunity activation. Computational immune simulations also showed potent activation of humoral and cellular immune responses, suggesting that the vaccine could protect across a range of genetically diverse populations. Designed to address the challenge of HCV's variable and highly conserved nature, this vaccine aims to target HCV immune response while minimizing virus escape effectively. The study also highlights the success of computational vaccinology in expediting vaccine development in a time and cost-efficient manner. The proposed vaccine construct shows significant potential, and further studies are warranted to assess its immunogenic properties, safety, and efficacy. Comparative molecular dynamics simulations of the apo-receptor, vaccine construct, and their complex revealed that binding induces structural stabilization and dampens flexibility at key interface residues. These results validate the docking predictions and underscore the robustness of the designed vaccine-TLR5 interaction. This study generates further understanding toward the goal of developing a broad prophylactic strategy against HCV that is readily available and potentially amenable to future clinical use, offering hope in the fight against HCV.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-025-00448-9.