Initial, positive results have been reported for a therapeutic vaccine candidate for treating patients with genital herpes. This first-in-class, investigational, protein subunit vaccine, GEN-003, is under development by Genocea Biosciences Inc.
Dr. Anna Wald, University of Washington professor of medicine and laboratory medicine in the School of Medicine and professor of epidemiology in the School of Public Health, is among those leading clinical studies of GEN-003. The trials are also taking place at six other centers in the United States.
One of several components of the vaccine was designed at the UW in Dr. David Koelle’s lab in the Division of Allergy and Infectious Diseases, Department of Medicine. Genocea, located near Boston, is a clinical-stage biopharmaceutical company for the discovery and development of T cell vaccines to prevent and treat infectious diseases.
T cells, a type of white blood cells, generate immune responses to pathogens and are important in controlling infections. T cell vaccine research is trying to find safe, effective ways to spur this protective reaction.
Wald and her team presented the initial findings of the first-in-human clinical trial of the novel GEN-003 T cell vaccine Sept. 12 at a session of the Interscience Conference on Antimicrobials Agents and Chemotherapy in Denver.
The team reported results from the Phase 1/2A clinical study. The ongoing Phase 1/2A clinical trial of GEN-0300 is a double-blind, placebo controlled, dose escalation study to evaluate safety and measure the immune response generated by the candidate vaccine. The study enrolled 143 volunteers with moderate-to-severe recurrent genital herpes.
Genocea plans to move into Phase 2 of this trial in 2014 to further evaluate GEN 003’s safety and effectiveness in a larger group of patients.
Genital herpes is a sexually transmitted disease caused by herpes simplex virus type 2. The infection can provoke recurring episodes of painful genital sores. An estimated 50 million to 60 million Americans are affected. At present, no vaccine is approved to prevent or treat genital herpes.
At unpredictable times in those carrying the infection, the herpes virus will come out of hiding and surface on the genitals, sometimes producing blisters and discomfort, and sometimes arising without any noticeable symptoms. This surfacing is called viral shedding. Shedding can spread the infection to others during sexual relations or during birth. Viral shedding is a marker both of the risk of recurrence and the transmission of infection.
Data from planned analysis of the Phase 1/2a clinical study showed that patients who received three doses of GEN-003 had reductions in the frequency of viral shedding of up to 51 percent. The vaccine is administered through an arm muscle injection. Patients who received a placebo had no decline in viral shedding.
The results also demonstrated that immunization with GEN-003 is associated with activation of T cell immunity. In those receiving the vaccine candidate, T cell immune responses increased more than 20 times to one vaccine antigen and more than 10 times to another antigen. The vaccine candidate also increased neutralizing antibodies to the herpes simplex 2 by five times greater than baseline amounts. The vaccine candidate was, overall, well tolerated by patients.
“These are the first data that provide compelling evidence that a vaccine administered to people with genital herpes can affect their infection,” Wald said. “We are excited that GEN-003 reduced viral shedding as this finding paves the way for future trials that will measure the impact on clinical outbreaks. The ability to reduce viral shedding is critical, as that is the main driver of transmission of HSV-2 to sexual partners and newborns.”
The first-in-human clinical trial was not designed to test whether GEN-003 lessens symptoms or lowers how often a breakout occurs. However, an exploratory analysis suggested that the interval between the first immunization with GEN-003 and the next recurrence of genital herpes might be longer in those receiving the actual candidate vaccine, rather than the placebo injection.
“The initial results are unprecedented in the clinical development of vaccines for herpes simplex virus-2,” noted Chip Clark, president and CEO of Genocea. “We are proud to be pioneers in the field of T cell-directed vaccines. We will complete this study and continue clinical development of GEN-003 with urgency, in order to bring this promising treatment to a large patient population that is in dire need of an approved vaccine that can prevent or treat their disease. “
Genocea developed the proprietary platform ATLAS, which can identify protective T cell antigens in people exposed to a pathogen. ATLAS mimics the human immune response. ATLAS was instrumental in developing GEN-003.
The vaccine contains, among other components, a proprietary adjuvant, trademarked Matrix-M. licensed from Novavax, Inc. The adjuvant has a product that, in previous clinical studies, has been shown to stimulate B and T cell immune responses.
Note: Dr. Wald is enrolling women infected with herpes simplex virus 2 in a study to see whether the drug tenofovir, given orally or as a vaginal gel, reduces genital shedding of the virus. Reducing the frequency of viral shedding is the first step to showing that a drug can reduce outbreaks or, potentially, sexual transmission to partners. Tenofovir has been shown in some studies to reduce the risk of acquiring HIV, and in some studies there was also a reduction in the frequency of HSV-2 acquisition, but this is the first time that it is being tested as a drug specifically for HSV-2. To learn more about the study, visit the UW Virology Research Clinic site.