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September 20, 2019

Penn researchers closing in on a possible genital herpes vaccine

Vaccine has proven effective in mice, guinea pigs

A genital herpes vaccine being developed by researchers at the University of Pennsylvania has proven effective in mice and guinea pigs. 

The next step is getting approval from the U.S. Food and Drug Administration to begin human trials. 

"We're optimistic that it will go forward," said Dr. Harvey Friedman, a herpes virologist. "There's a biotech company that has expressed interest. I'm hoping that will be the next big step for us."

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Friedman has been researching herpes for much of his 44-year career at Penn Medicine. As part of his latest study, published Friday in the journal Science Immunology, researchers took a two-pronged attack in developing a potential vaccine.

Their vaccine is designed to prevent the herpes virus from entering the cells it needs to grow – a fairly standard approach, Friedman said. But the vaccine also aims to block the proteins the virus needs to escape the immune system's response. 

No previous attempts at a genital herpes vaccine have been as effective theirs, Friedman said. 

"There's no guarantee that because we're doing great in mice and guinea pigs that it will work in humans," Friedman said. "But what we can say is that we're doing better in mice and guinea pigs than anyone else ever has done. The next step is how will it do in humans?"

Genital herpes is the most common sexually-transmitted disease, infecting about 14 percent of Americans between the ages of 14 and 59. 

Many infected people do not realize they have herpes because they do not display any symptoms, which typically appear as sores around the genitals, according to the U.S. Centers for Disease Control and Prevention. The virus also can lay dormant for periods of time. There is no known cure, but some medications can prevent or shorten sore outbreaks. 

"This vaccine is aimed at trying to prevent herpes," Friedman said. "We're not doing this as a treatment to those that are already infected. The target population would be adolescents before they're sexually active."

The vaccine stimulates three types of antibodies – one that prevents the herpes virus from entering cells and two more that ensure the virus does not halt natural immune system protections. 

To do so, researchers used a specific messenger RNA that can create the proteins needed for a strong immune response. 

Typically, the body breaks down RNA very quickly, Friedman said. But one of his fellow researchers, Dr. Drew Weissman, came up with a novel delivery method that enables the RNA to produce the proteins for about a week.  

Researchers gave the vaccine to 64 mice before exposing them to genital herpes. After 28 days, all but one of the mice were found to have sterilizing immunity – the strongest form of immunity. The 63 mice showed no trace of herpes infection after exposure. 

Researchers also tested 10 guinea pigs, which respond to herpes infections in a way more similar to humans. None of them developed genital lesions. Only two displayed signs of infection, but it was not in a form in which the animals could transmit the virus. 

The vaccine not only prevented the animals from developing lesions, but it also kept the virus from establishing dormancy. That dormancy allows people to transmit herpes without knowing they have it.

"It's as if nothing had happened," Friedman said. "The virus didn't do a damned thing. Nothing. That's remarkable, actually. That would be the ultimate goal of a human vaccine."

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