Herpes Simplex Virus Infections and Vaccine Advances

Herpes simplex viruses belong to the subfamily Alphaherpesvirinae and the genus Simplexvirus and have the capacity to establish latent infections in sensory ganglia of humans. Intermittent reactivation of the virus can cause retrograde transportation to the dermatome where initial infection occurred, the virus crosses into the stratified squamous epithelium where it starts replicating again. Herpes simplex viruses that cause infections in humans are HSV-1 (infection of the skin and oral mucosa) and HSV-2 (sexually transmitted infection of the genital tract). Despite almost a century old efforts to develop vaccine against HSV viral infection, results from clinical trials in humans have been disappointing. Three main approaches were used to develop the vaccine: glycoprotein vaccine (gB and gD), mutated inactivated live virus and DNA vaccines. Although all vaccine candidates showed excellent results in animal models, significant protection was not seen in human clinical trials. This not only questions the validity of the animal models but also calls for a change in the current strategies in designing future vaccine candidates.

In designing the vaccine candidates very little attention was devoted to the immune evasion mechanisms of the virus that are the main reason that the virus is able to persist and to reactivate when immune responses weaken.

Keywords: Herpes, alphaherpesviridae, sensory ganglia, HSV-1, HSV-2, glycoprotein, vaccine, immune evasion, latent infection, skin infection, genital tract infection, viral envelope, DNA vaccine, STD, Simplexvirus, gB, gD, CD8+ T cells exhaustion, HERPEVAC, ICP4.