Scientists Frustrated in Search for Genital Herpes Vaccine

October 29, 2009 by admin

Experts say a lack of funds is slowing attempts to find a truly effective vaccine against genital herpes, a sexually transmitted disease that can be devastating for the one in five Americans over 12 who carry the virus.

Genital infection with the herpes simplex viruses (HSV) 1 or 2 is not just an inconvenience, doctors note. It is a painful, recurrent illness that causes psychological distress, raises health risks for newborns, and boosts the carrier’s odds for a much more deadly virus, HIV.

And even as the Herpevac trial — the first major publicly funded trial of a preventive vaccine — is set to get under way, a leader of that trial says the vaccine, even if successful, would not be the solution to the herpes epidemic.

“The Herpevac trial is a vaccine that is only going to affect the [uninfected] adolescent woman,” said Dr. Lawrence Corey, head of infectious diseases and virology at the University of Washington, in Seattle. “It is not going to be effective in men or in those who are HIV-positive. We need to do better.”

Prior, expensive failures have made the drug industry skittish about funding herpes vaccine trials, however. So, despite the fact that most adult Americans either have HSV-1 or 2, or are at very high risk of contracting it in their lifetime, not enough is being done to stop the pathogen.

“I would say that, at the moment, the Genital Herpes vaccine is a field that does not have much interest, does not have much money,” Corey said. “The need for an HSV vaccine is really substantive, but there is not much of a program in the industrialized, developing world to develop such a vaccine.”

Part of the problem lies in the complexity of the virus. While simpler viruses such as the flu simply mutate their outer coats to evade the human immune system, HSV and other persistent viral infections are much more stable.

However, they have another secret weapon. Compared to other viruses, HSV 1 and 2 “have a lot more genes and gene products that are redirecting and subverting the [host] immune response,” Corey explained.

Although the two strains are similar and can infect either mouth or genitalia, HSV-1 is the prime cause of oral herpes (cold sores and fever blisters), while HSV-2 is the usual source of genital infections.

Another tactic keeps herpes well-shielded from immune attack. Unlike pathogens that spread in readily accessed blood, HSV hides out in nerve cells called dorsal ganglia, located in the back. Specific triggers, such as sun exposure or stress, can send the virus traveling through nerve pathways to mucosal sites of activity in the genitalia, mouth and even eyes.

These nerve cells are “a protected site, immunologically,” explained Dr. Lawrence Stanberry, director of the Sealy Center for Vaccine Development at the University of Texas Medical Branch in Galveston. “Needless to say, we don’t like to have our immune system attacking our nerves,” he said, so vaccines with that kind of reach are hard to develop.

And yet, progress is being made. The Herpevac trial, funded by the U.S. National Institutes of Health and drug maker GlaxoSmithKline, is focused on a preventive vaccine aimed solely at uninfected women. Preliminary, phase III studies completed last year found the vaccine to be 73 percent effective in shielding young women from infection after exposure to HSV-2.

A 73 percent effectiveness rate may not sound all that impressive, but Stanberry — also an investigator on the Herpevac trial — said no one is expecting 100 percent immunization.

“What one hopes for with a vaccine is that you get very high rates of effectiveness and then very broad uptake of the vaccine [in the population],” he explained. “So then, if almost everyone gets immunized, then the disease simply doesn’t circulate in the population to the same extent.”

Reducing the “pool” of available virus will be vital to lowering the infection rate, researchers say, because the Herpevac shot does not protect uninfected men and cannot eliminate HSV from people who are already infected.

The Herpevac trial is currently wrapping up recruitment of 7,000 healthy, HSV-negative U.S. women between the ages of 18 and 30. Participants will receive either the vaccine or a placebo and then be followed for 18 months to see if they become infected.

Stanberry said final results from the trial should be available by 2009, and — if the vaccine proves effective — a shot might be approved by 2010.

However, like most modern vaccine trials, the Herpevac trial relies on a piece or “subunit” of HSV to prime the human immune system against incoming virus.

Another researcher is advocating the use of the live — but greatly weakened — form of the virus, instead.

The problem with the subunit approach is that its effects don’t last, said William Halford, a virologist at Montana State University, in Bozeman. “Once you deliver it into someone’s body, it’s there, but, in a few weeks, it is gone,” he said.

Live virus vaccines have a long and effective history. In fact, one of the few effective vaccines against any herpes strain — the chickenpox/shingles (herpes zoster) shot — was developed from live virus back in the 1960s.

Since that time, doctors have gotten more skittish about injecting people with a live form of the virus, however, so the subunit approach took precedence.

But Halford believes it is time to revisit the idea of a live virus herpes vaccine.

“All we really have to do is to figure out a way to take away some of the genes or proteins that the virus needs to cause actual disease,” he said. In other words, people would be infected with a very weak form of HSV, one that is sufficient to trigger a sustained immune response but too frail to trigger disease outbreaks.

Halford is specifically investigating a protein in HSV called ICP0. “If I take away the gene that codes for that protein, the virus is really weakened,” he said.

The approach is controversial, but Corey believes it could have promise. “I certainly think that the live attenuated virus is a viable approach to talk about,” he said.

Funding will be the real challenge, however, whatever the vaccine strategy. According to Corey, a series of expensive failures over the past two decades has dampened the enthusiasm of industry to invest in HSV vaccine research.

“I can give my own scenario in which we worked with [drug maker] Chiron and spent seven years and a lot of money — decapitalizing the company by 25 percent — on an antibody-based vaccine,” Corey said. “At the time, we thought it would be sufficient to work, but it didn’t.”

So, with the private sector waiting on the sidelines, public funding becomes key.

“I think there needs to be more money from the publicly funded institutions — whether they be foundations, the NIH or the National Research Council, in vaccine development,” Corey said.

“We also need to do more in defining a real path of success for a Genital Herpes vaccine,” he added. “Once some pathway of success becomes defined, then you’ll see the pharmaceutical companies move forward.”


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