Distal and local mucosal immunization with a BoHV-4-based vector delivering CpHV-1 gD confers protection against intravaginal CpHV-1 challenge in goats

Effective vaccines against sexually transmitted pathogens must elicit protective immunity at mucosal surfaces, particularly within the female reproductive tract. Caprine herpesvirus 1 (CpHV-1) causes genital disease, reproductive failure, and neonatal mortality in goats and provides a biologically relevant large-animal model for human genital herpesvirus infection. Here, we evaluated a mucosal vaccination strategy based on a bovine herpesvirus 4 (BoHV-4) vector expressing the CpHV-1 immunodominant glycoprotein D (BoHV4-A-gD(cp)gD(106)ΔTK). Goats were immunized via the intravaginal or intranasal route using a prime–boost regimen and subsequently challenged intravaginally with virulent CpHV-1. Ex vivo tissue analyses showed efficient transduction of nasal mucosa and limited vaginal transduction restricted to the cervical region. Despite these differences, both immunization routes conferred complete protection against disease. Vaccinated animals showed no fever or genital pathology following challenge, in contrast to unvaccinated controls. Viral shedding was significantly reduced in vaccinated goats, with intravaginal immunization providing superior control of genital virus excretion. Both routes induced CpHV-1–specific systemic antibody responses, including functional neutralizing antibodies, with higher neutralizing titers observed after intranasal vaccination. These findings demonstrate that BoHV-4–based vectors can induce robust protective immunity against genital herpesvirus infection when delivered via either local or distal mucosal routes. The results highlight the importance of mucosal vaccination strategies and support the versatility of BoHV-4 as a vaccine platform for sexually transmitted infections. This study further establishes the goat–CpHV-1 model as a valuable translational system for the preclinical evaluation of mucosal herpesvirus vaccines.