Herpes simplex viruses: is a vaccine tenable?

Human herpes simplex virus (HSV) infections have been documented since ancient Greek times. Greek scholars, notably Hippocrates, used the word “herpes,” meaning to creep or crawl, to describe spreading cutaneous lesions. Over the ensuing centuries, the clinical manifestations were described, including a distinction between genital and orofacial herpes, accounting for the designation of HSV-1 and HSV-2. Importantly, these viruses have a unique propensity to establish latency and recur over time, in spite of specific host immune responses, making successful vaccine development a challenge. The spectrum of disease caused by HSV includes primary and recurrent infections of mucous membranes (e.g., gingivostomatitis, herpes labialis, and genital HSV infections), keratoconjunctivitis, neonatal HSV infection, visceral HSV infections of the immunocompromised host, encephalitis, Kaposi varicella-like eruption, and an association with erythema multiforme. As it relates to genital herpes, 22% of the general population is infected with HSV-2, and the seroprevalence is even higher: 30–50% in patients attending sexually transmitted diseases clinics. Here, we will focus on HSV vaccine development with specific reference to translational molecular biology.