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January 5, 2012

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QUESTIONS AND ANSWERS
The Herpevac Trial for Women

Updated January 5, 2012


1.   What is the Herpevac trial for women?
   

The Herpevac trial for women is a clinical study investigating a vaccine to protect women against genital herpes disease. The trial, which began in 2002 and concluded in 2010, was conducted at 50 sites in the United States and Canada and was sponsored by GlaxoSmithKline (GSK) Biologicals in cooperation with the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. The study chair is Robert Belshe, M.D., director of the Center for Vaccine Development at the Saint Louis University School of Medicine in Missouri.

2.   How many participants were involved in the study?
   

The Herpevac Trial for Women involved 8,323 women ages 18-30. At the time of their enrollment, the study participants were free of the two common types of herpes simplex viruses (HSV): HSV-1, the primary cause of cold sores and an increasing cause of genital herpes, and HSV-2, the common cause of genital herpes. Approximately 31,000 women were screened in order to identify eligible participants.

3.   What was the study’s design?
   

The study was a randomized, double-blind, controlled Phase III clinical trial. Participants were randomly assigned to receive either the investigational herpes vaccine or a version of Havrix, an FDA-approved, licensed vaccine to protect against hepatitis A. This was done to give all participants an opportunity to be protected against either genital herpes or hepatitis A. GSK developed the candidate herpes vaccine and is also the manufacturer of Havrix.

The investigational herpes vaccine is a subunit vaccine containing a glycoprotein from HSV along with an adjuvant to boost immune response. The Havrix vaccine administered to study participants was provided at a lower dose and smaller volume than it is routinely provided in medical practice. This was done to ensure that the vaccine could be administered in the same number of doses as the candidate herpes vaccine.  Each volunteer was vaccinated at the beginning of the study and again after one month and six months following the first injection. The participants were followed for 20 months after the initial injection and evaluated for HSV infection and genital herpes disease. Throughout the study, participants were regularly counseled on how to reduce their risk of acquiring HSV.

4.   What were the results of the trial?
   

The trial was successfully conducted according to protocol and met statistical targets in terms of enrollment and participant follow up. The vaccine proved to be well-tolerated and its safety profile was similar to that observed in previous trials. According to the initial data analysis publicly announced in September 2010, the trial produced a point estimate of overall vaccine effectiveness of 20 percent with a confidence interval that included zero. In other words, the vaccine was not effective at preventing genital herpes disease among the study population of women. At that time, study collaborators stated that evaluation of the trial data would continue and that a more detailed analysis would be provided at a later time.

A subsequent, more detailed analysis published in the New England Journal of Medicine on Jan. 5, 2012, found that the investigational vaccine provided some protection against HSV-1, although it did not protect against HSV-2. Specifically, there were 58 percent fewer cases of genital herpes caused by HSV-1 and 35 percent fewer HSV-1 infections among women who received the investigational vaccine, compared to those who received the control vaccine. The recent analysis also found that among women enrolled in the control group, HSV-1 caused more cases of genital herpes than HSV-2. 

Reference:
RB Belshe et al. Efficacy results of a trial of a herpes simplex vaccine. New England Journal of Medicine 366(1):26-35 (2012).

5.   Why was the trial important?
   

The Herpevac Trial for Women produced important scientific information to guide future research toward a vaccine to prevent genital herpes.  It also provided emerging data about genital herpes and the changing role of HSV-1 in infection.

An estimated one in four women in the United States has genital herpes, making it one of the most common infectious diseases. HSV, the cause of genital herpes disease, may be transmitted through sexual or other skin-to-skin contact, and can be spread even when the infected individual shows no symptoms. Once in the body, HSV migrates to nerve cells and remains there permanently where it can reactivate to cause painful outbreaks in the infected individual. HSV can cause severe illness in infants born to HSV-infected women, and the virus has been identified as a risk factor for HIV transmission in adults. There is no cure for herpes infection, and there is no vaccine to prevent it.

When the investigational vaccine was tested in two earlier studies involving fewer men and women who did not have genital herpes but whose sexual partners were known to be infected, the candidate vaccine prevented genital herpes disease in more than 70 percent of the female volunteers but had no clear effect in men. Further, the candidate vaccine reduced by roughly 40 percent the risk of developing antibodies to herpes, which are used as an indicator that a person has been infected with HSV. These studies formed the basis for conducting the larger Herpevac study. Results of these two earlier studies were published in November 2002 in the New England Journal of Medicine.

Reference: LR Stanberry et al. Glycoprotein-D-adjuvant vaccine to prevent genital herpes. New England Journal of Medicine 347(21):1652-1661 (2002).

Though it failed to reach its primary goal, the Herpevac Trial for Women produced important scientific information to guide future research toward a vaccine to prevent genital herpes. The researchers suspect that the differences between the 2002 studies and the Herpevac Trial were due to immunologic and behavioral differences in the populations studied, which may have affected participants’ protection from HSV-1 and HSV-2.  

The trial results also provided emerging data about genital herpes and the changing role of HSV-1 in infection. Although HSV-1 is typically associated with cold sores and HSV-2 with genital lesions, HSV-1 has become a growing cause of genital disease, an observation echoed in this analysis. Among women enrolled in the control group of the Herpevac trial, HSV-1 was found to cause more cases of genital herpes than HSV-2.

6.   How was participant safety monitored during the trial?
   

Participant safety was closely monitored throughout the trial, both by the study investigators and by a data and safety monitoring board (DSMB). The DSMB is an independent committee composed of clinical research experts, herpes virus experts, and statisticians that provides additional oversight of a clinical study. The DSMB regularly reviews data while a clinical trial is in progress to ensure the safety of participants and that any benefits shown in the study are quickly made available to all participants.

The investigational herpes vaccine used in the trial had been previously tested in more than 7,000 volunteers; results from these studies suggested that it was well-tolerated and safe.

7.   Was there any risk to participants that the vaccine could cause herpes infection?
   

No. The herpes vaccine formulation used in the study did not contain live virus and was incapable of infecting participants with herpes virus. The candidate vaccine contained only a specific fragment of a herpes virus protein to stimulate immune responses.

8.   Will researchers continue to analyze the data from the Herpevac Trial to better understand the results?
   

Yes. Researchers will continue to examine serum samples from the Herpevac study to better understand why the vaccine protected women from genital disease caused by HSV-1, but not HSV-2.
   
For more information about the Herpevac study, see Study Finds Genital Herpes Vaccine Ineffective in Women. For additional information about genital herpes, visit NIAID's Genital Herpes website.


NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at www.niaid.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Last Updated January 05, 2012

Last Reviewed September 29, 2010