Design of a Recombinant Multi-Epitope Subunit Vaccine Targeting Glycoproteins of Herpes Simplex Virus Type 2 Using an Immunoinformatics Approach

Herpes simplex virus type 2 (HSV-2) is a major global cause of genital herpes, characterized by its lifelong latency and high transmission rate, yet no licensed vaccine currently exists. This study aimed to design a recombinant multi-epitope subunit vaccine targeting HSV-2 envelope glycoproteins (gB, gC, gD, gH, and gL) using an immunoinformatics-guided approach. A total of 37 epitopes comprising cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell targets were selected based on high antigenicity and confirmed to be non-allergenic and non-toxic. The final construct included adjuvants and immunostimulatory elements to enhance immune recognition. Structural analysis showed a favorable molecular weight of 92.7 kDa, high stability (instability index 39.16), and strong hydrophilicity (GRAVY score -0.367). Validation of the 3D model yielded an ERRAT score of 74.77 and 82.60% of residues within the most favored regions in the Ramachandran plot, indicating a high-quality and reliable conformation. Molecular docking simulations demonstrated strong binding affinities of the vaccine construct with MHC class I, MHC class II, TLR2, and TLR4. Highest binding affinity value of -335.03 kcal/mol for TLR4, supported by the formation of optimal hydrogen bonds and salt bridges indicating potential to elicit robust adaptive and innate immune responses. These findings indicate that the designed vaccine is structurally robust, immunologically promising, and suitable for further in vitro and in vivo evaluation against HSV-2 infection.