UNLABELLED: Herpes simplex virus type-1 (HSV-1), the etiological agent of sporadic encephalitis and recurring oral (sometimes genital) infections in humans, affects millions each year. The evolving viral genome reduces susceptibility to existing antivirals and, thus, necessitates new therapeutic strategies. Immunoinformatics strategies have shown promise in designing novel vaccine candidates in the absence of a clinically licensed vaccine to prevent HSV-1. However, to encourage clinical translation, the HSV-1 pan-genome was integrated with the reverse-vaccinology pipeline for rigorous screening of universal vaccine candidates. Viral targets were screened from 104 available complete genomes. Among 364 proteins, envelope glycoprotein D being an outer membrane protein with a high antigenicity score (> 0.4) and solubility (> 0.6) was selected for epitope screening. A total of 17 T-cell and 4 B-cell epitopes with highly antigenic, immunogenic, non-toxic properties and high global population coverage were identified. Furthermore, 8 vaccine constructs were designed using different combinations of epitopes and suitable linkers. VC-8 was identified as the most potential vaccine candidate regarding chemical and structural stability. Molecular docking revealed high interactive affinity (low binding energy: - 56.25 kcal/mol) of VC-8 with the target elicited by firm intermolecular H-bonds, salt-bridges, and hydrophobic interactions, which was validated with simulations. Compatibility of the vaccine candidate to be expressed in pET-29(a) + plasmid was established by in silico cloning studies. Immune simulations confirmed the potential of VC-8 to trigger robust B-cell, T-cell, cytokine, and antibody-mediated responses, thereby suggesting a promising candidate for the future of HSV-1 prevention. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-024-04022-6.