Genital herpes is an incurable, lifelong sexually transmitted disease that affects more than 600 million people worldwide. Patients infected with genital herpes experience recurring, painful genital sores and suffer from considerable psychological distress due to stigmas associated with the disease. Genital herpes is particularly severe in immunosuppressed patients, increases the risk of HIV transmission and poses a significant risk to newborns if it is transmitted from mothers during birth.
Cause and Diagnosis
Genital herpes is caused by herpes simplex virus (HSV), which exists in two forms, HSV-1 and HSV-2:
- While both forms of HSV can cause genital herpes, HSV-2 causes the majority of disease, although prevalence of HSV-1 genital herpes is rising more rapidly.
- Transmission occurs through contact with oral or genital fluids or mucous membranes
- The diagnosis of genital herpes may be confirmed by a viral culture or DNA test from a herpes sore. Tests can also differentiate between HSV-1 and HSV-2.
- Most people with genital herpes infection are unaware of their infection, either because they have no symptoms or have mild symptoms, which are mistaken for another condition.
Genital Herpes Lesions and Viral Shedding
When the virus is transmitted from one person to another, visible signs of infection begin to appear on average four days after transmission in the form of blisters, or lesions, usually on or around the genitals and rectum. Lesions can also occur around other mucus membranes such as the mouth or eyes.
The first outbreak of genital herpes may be more severe, with longer lesion duration, increased viral shedding and accompanying symptoms including fever, headache, painful urination and swollen lymph nodes. In rare cases, genital herpes can cause serious complications such as blindness, encephalitis (inflammation of the brain), and aseptic meningitis (inflammation of the linings of the brain).
Once infected with HSV-2, an individual may experience outbreaks several times a year for the rest of his or her life - these manifestations of the disease are linked to its infection cycle:
- Upon entering the body, the virus creates a small, permanent colony of viral particles that lies dormant between outbreaks. The infection hides from the immune system in a nerve root (ganglion) at the base of the spine, in a state called latency.
- Periodically the virus reactivates and begins to replicate and move back down the nerve cell, into the epithelial (skin) cells around the genitalia and/or into the mucosa of the genitals. Once the virus infects skin or mucous membrane cells, it may be detectable even if no herpes lesions are present. This is called asymptomatic viral shedding and is the point of the infection cycle when transmission occurs most frequently.
- If the magnitude or duration of viral shedding is great enough, the typical painful visible lesions of genital herpes may appear on the genitalia.
A Widespread Disease with Multiple Risk Groups
People with HSV-2 can still be highly infectious even if they are not experiencing noticeable symptoms. Additionally:
- HSV-2 affects one out of six people between the ages of 14 to 49 in the United States
- Roughly 80 percent of infected individuals aged 14 to 49 in the United States go undiagnosed because their symptoms are so mild or are mistaken for another skin condition such as a yeast infection, “jock itch,” or an insect bite.
- Nationally, women have a higher prevalence than men (21 percent vs. 11.5 percent) because male-to-female transmission is easier than female-to-male transmission.
- Infants born to women with HSV-2 infection can acquire a systemic HSV-2 infection during delivery, and the risk of acquiring neonatal herpes is highest when genital lesions are present on the mother at the time of delivery.
Neonatal herpes is a severe form or the disease that includes skin rash, inflammation of the brain, infection of the eye, and possibly death.
Today’s Treatment Landscape
While available antiviral treatments can help prevent and shorten outbreaks, there is a significant unmet need for therapeutic approaches that better control symptoms, viral shedding (the active viral state when transmission risk is greatest), and risk of disease transmission. Antivirals on the market include:
- Acyclovir or Zovirax® by GlaxoSmithKline
- Valacyclovir or Valtrex® by GlaxoSmithKline
- Famciclovir or Famvir® by Novartis
All three drugs can be used as episodic therapy (taken during outbreaks) or suppressive therapy (taken daily to hold genital herpes in check). However, the incomplete control of genital lesions and transmission risk, expense and the perceived inconvenience of taking a daily medication are hurdles for long-term disease management. Clinical studies are underway to evaluate potential new therapies for genital herpes. Immunity through T cells is believed to be particularly critical to the control and possibly prevention of genital herpes infections.
First-in-Class Therapy: GEN-003
Genocea’s lead clinical candidate is GEN-003, a first-in-class immunotherapy intended to reduce the transmission risk and clinical symptoms of genital herpes by inducing both a T cell and B cell (antibody) immune response. GEN-003 has demonstrated first-in-class results to date by showing statistically significant reductions in clinical signs of genital herpes and viral shedding.
If approved, we believe GEN-003 would be the first therapeutic vaccine or immunotherapy for managing genital herpes infections.