Integrative immunoinformatics and molecular modeling approaches for the rational design and in silico validation of a multi-epitope vaccine candidate against human herpesvirus 7.

Human herpesvirus 7 (HHV-7) is a widespread β-herpesvirus associated with various clinical manifestations, particularly in immunocompromised individuals. Despite its high prevalence, no licensed vaccine is currently available. Advances in immunoinformatics and computational vaccinology provide efficient strategies for the rational design of targeted immunogens. Comprehensive analysis of HHV-7 protein sequences was performed to identify potential T-cell (MHC class I and II) and B-cell epitopes using an established immunoinformatics pipeline. Selected epitopes were assembled into a multi-epitope vaccine construct incorporating suitable linkers and an immunostimulatory adjuvant. The designed construct was evaluated for antigenicity, allergenicity, solubility, and physicochemical properties. The final multi-epitope vaccine construct (26.65 kDa) demonstrated favorable physicochemical characteristics, including predicted solubility and structural stability. Structural validation showed a high-quality model with an ERRAT score of 93.77 and 85.5% of residues located in favored regions of the Ramachandran plot. Immune simulation predicted a robust Th1-biased immune response characterized by elevated IFN-γ and IL-2 production, along with significant IgM and IgG responses. The construct exhibited an estimated 49.02% global population coverage for MHC class II alleles. These findings are consistent by demonstrating promising structural integrity and predicted immunogenicity. This study presents an in silico-designed multi-epitope vaccine candidate against HHV-7 with favorable structural, immunological, and population coverage characteristics. While computational predictions indicate strong immunogenic potential, experimental validation through in vitro and in vivo studies is required to confirm its efficacy and safety.