Status of Vaccine Research and Development of Vaccines for Herpes Simplex Virus Prepared for WHO PD-VAC I. About the Disease and Pathogen

The Herpes simplex viruses are responsible for a broad-spectrum of diseases affecting all age groups across the developed and developing world. The viruses are members of the herpesvirus family, which also includes the human pathogens Varicella-Zoster virus, Epstein-Barr virus, Cytomegalovirus, Human herpes virus -6 and -8. Herpes simplex virus type -1 (HSV-1) and -2 (HSV-2) are serotypically differentiated based on genetically different surface glycoproteins, but both types are capable of infecting the oral or genital mucosa and causing lifelong, incurable infections (1). The virus infects epithelial cells at skin or mucosal surfaces, and then infects nerve endings, travels up the nerve axon, and establishes persistent infection in the trigeminal (HSV-1) or lumbosacral (HSV-1 or HSV-2) ganglia, where it is protected from the host immune response. The virus returns down the axon to cause oral or genital ulcers or asymptomatic viral shedding. Asymptomatic viral shedding occurs frequently, and during these periods the virus is transmissible. The ability of the virus to be acquired and transmitted in the absence of symptoms allows it to spread efficiently and silently throughout the population. As most infections are subclinical, disease incidence data are thought to underestimate the magnitude of HSV infection.