IN THE EARLY '90S, scientists working on the herpes simplex viruswere almost sure a vaccine was just around the corner. The University of Washington's preeminent Virology Research Clinic was one of a number of clinics testing the hoped-for vaccine on the heels of smaller studies showing promising results. "Herpes may be history as early as 1997," this paper speculated five years ago.
Unfortunately, as the clinics involved announced last fall, the vaccine didn't work. "It shattered a lot of people's hopes about what could be done," says Stephen Sacks, professor of pharmacology and therapeutics at the University of British Columbia.
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Disillusionment has turned to cautious optimism, however, as the UW clinic proceeds with two new studies. One is what its medical director, Dr. Anna Wald, calls a "very, very preliminary" look at a more sophisticated type of vaccine. The other, more encouraging study examines whether an already common herpes drug can be used to prevent transmission—a feat doctors never before attempted.
The studies are especially important given that one in five Americans has genital herpes. According to an October New England Journal of Medicine report, the disease has spread fastest among white teens—possibly because they feel safe enough fromAIDS to forgo safe sex, and because condoms don't always cover infected areas.
Moreover, up until five or so years ago, doctors commonly told herpes patients they had little chance of passing the virus unless they experienced the itching and sores associated with outbreaks. That accepted wisdom has been turned on its head by recent research, pioneered at the UW clinic, showing that most transmission occurs when such symptoms are not present. Many people don't even know they have the virus when they pass it on.
The clinic has also shown, however, that the drug acyclovir, now used only to treat recognized outbreaks, can also suppress invisible but infectious "subclinical shedding." "That led to the concept that maybe it could be used to prevent transmission," says Wald.
Her clinic is one of 25 sites worldwide chosenby the drug company Glaxo Wellcome to test an acyclovir derivative called valacyclovir. Wald's clinic will follow 150 couples—each with only one infected partner—for eight months to see whether transmission occurs. Half the infected participants will take a valacyclovir pill once a day, and half will take placebos.
WHILE MOST RESEARCHERS in the fieldexpect positive results, that outcome isn't certain, since valacyclovir doesn't eliminate all traces of the virus. "We don't know how much virus it takes to transmit," says Dr. Hunter Handsfield, a UW medical professor who directs the STD control program of the SeattleKing County Health Department and is drawing up a herpes prevention plan for the Centers for Disease Control and Prevention.
And even if the results are positive, Handsfield notes that "these pills aren't cheap. You're talking about a few hundred dollars a year." Rather than take a daily pill indefinitely, he suggests, many people will use the drugs in special circumstances. Crucially, a herpes-infected man could take them during his wife's pregnancy, given that if his wife should become infected, she could pass the virus on to the baby, with possibly fatal consequences.
A vaccine would of course be a far easier way to prevent transmission: one shot for life instead of daily pills. And indeed, the UW clinic, sponsored by the drug company Apollon, is looking at a new vaccine that uses gene pieces to stimulate the body into making a virus-fighting protein. Wald says this process "may evoke a broader immune response" than the old vaccine, which injected a ready-made piece of that protein without getting the body involved in making it.
But the new vaccine, one of several variations under development, is years away from market at best. This two-year, 40-person trial—which has been going on for a year but still seeks more participants—marks the first time it has been tested on humans. Even if it succeeds, many more tests will be required for federal approval. But after the demoralizing failure of the old vaccine, Wald sees the effort itself as significant: "People haven't given up on the field."
Volunteers interested in participating in the UW studies should call 206-720-4340.
The U of W's herpes research page