An experimental genital herpes vaccine developed by Harvard Medical School researchers is being tested in an early-stage clinical trial conducted by a branch of the National Institutes of Health.
There is currently no vaccine to prevent genital herpes disease, a sexually transmitted infection caused by herpes simplex virus 1 (HSV-1) or 2 (HSV-2). Outbreaks of painful sores and blisters, which can be treated but not cured, alternate with silent periods when the virus retreats into neurons where it lies dormant until reactivated. HSV-1 commonly infects the mouth and lips, but it can also cause genital herpes.
About three-quarters of a million people are newly infected with genital herpes each year in the United States, causing suffering in adults and threatening the lives of infants born to infected women. HSV-1 can also cause blindness if recurrent infections spread to the cornea. If either HSV-1 or HSV-2 enters the central nervous system, it can lead to encephalitis.
In sub-Saharan Africa, where risk for HIV infection is high, as many as 80 percent of the population is infected with HSV-2.
“There’s a medical need to prevent herpes disease, but the biggest issue is that genital herpes increases the risk of HIV infection,” said David Knipe, HMS Higgins Professor of Microbiology and Molecular Genetics. “A genital herpes vaccine that prevented HSV-2 infection could reduce the risk of HIV infection.”
Creating a safe, effective vaccine has been difficult for scientists around the globe, mirroring the long parallel road toward an HIV vaccine. While some HSV vaccine candidates studied in animals have prompted the immune system to form antibodies to HSV, they couldn’t induce a T cell response that would also kill cells infected with the virus. Both lines of defense are needed, Knipe said. Other vaccine candidates that effectively mounted a dual immune response failed safety tests.
It was 20 years ago that Knipe took the first, indirect steps toward the experimental vaccine. While studying gene function in viruses, Knipe and his colleagues had genetically altered the virus so it could not make copies of itself. The mutant version of the virus enters cells, prompting both an antibody and T cell response, but it can’t multiply.
At the time, this approach ran counter to the dogma stating that viral vaccines must contain killed virus or weakened viral components to stimulate a durable immune response. Since then, these “replication-defective” viruses have been enlisted as smallpox vaccines and vectors for investigational HIV vaccines.
The current clinical trial, led by Lesia Dropulic of the National Institute of Allergy and Infectious Diseases, is testing an HSV-2 vaccine candidate manufactured by Sanofi Pasteur. Knipe is a consultant for Sanofi but he is not involved in the trial.
The NIAID researchers hope to enroll 60 adults, age 18 to 40, who will be divided into three groups: people who have previously been infected with HSV-1 and HSV-2 or only HSV-2; people who have previously been infected only with HSV-1; and people who have not been infected with either HSV-1 or HSV-2. Participants will be randomly chosen to receive three doses of the experimental vaccine or a placebo. Their safety will be monitored and their blood will be drawn to evaluate the vaccine’s ability to stimulate an immune system response to HSV-2.
The study is expected to conclude in October 2016.
“Although genital herpes is treatable, it is a lifelong infection that exacts a tremendous psychological and physical toll on the infected individual,” NIAID Director Anthony S. Fauci said in a statement announcing the clinical trial. “A protective vaccine would help to significantly reduce the spread of this all-too-common sexually transmitted infection.”