Immunoinformatics Design of Multi-Epitope Peptide-Based Vaccine Against Cyprinid Herpesvirus-3 (CyHV-3) Targeting Thymidine Kinase Proteins

Abstract

The common carp Cyprinus carpio is a freshwater teleost and is among the most economically significant fishes in aquaculture throughout the world. Taxonomically, C. carpio are a complex of species including subspecies Cyprinus carpio carpio. C. carpio are now threatened by Cyprinid Herpesvirus-3 (CyHV-3), the causative agent of Koi Herpesvirus Disease (KHVD), which causes severe morbidity and mortality in ornamental koi and common carp and can infect or be transmitted by other species. Despite these devastating circumstances, effective vaccinations or other medications for the control of KHVD are not readily available. For this reason, the aim of the current study was to formulate a multi-epitope vaccine against Cyprinid Herpesvirus-3 (CyHV-3) using an immunoinformatics approach. To assess the immunodominant T- and B-cell epitopes, the CyHV-3 proteomes were employed. Following a thorough evaluation, we constructed a strategy for vaccination employing four possible epitopes selected from among each of the three relevant epitope groups: cytotoxic T-lymphocyte, helper T-lymphocyte and linear B-lymphocyte. Important qualities used in the evaluation of the resultant vaccine are that it will be highly soluble, antigenic, immunogenic and non-allergenic. Among acceptable physicochemical qualities, the anticipated structure of the vaccine bears a close resemblance to that of the original protein. Additional considerations include a robust and sustained predicted binding between the vaccine and the Toll-Like Receptor (TLR9). Simulations of molecular dynamics confirm the likelihood of a strong binding stability and structural tightness. Moreover, the computer-generated immunological simulation revealed that the vaccine, when administered to fish, should induce immune responses comparable to those in real life. Finally, codon optimization based on Escherichia coli K12 produced favorable indications of GC content and acceptably high CAI value, as applicable to the cloning vector pET28+ (a). Overall, these results show that the proposed peptide vaccine is a promising option for CyHV-3 prophylaxis.