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Herpes Vaccine Fails to Protect Women
  By Michael Smith, North American Correspondent, MedPage Today Published: January 04, 2012

A once-promising vaccine against herpes viruses has failed in a large clinical trial, researchers reported.

The vaccine had markedly reduced the risk of genital herpes disease in women in so-called serodiscordant couples, in which one partner had the virus and other did not, according to Robert Belshe, MD, of St. Louis University in St. Louis, Mo., and colleagues.

But in a large study intended to mimic the general population of uninfected women, vaccine efficacy against disease was only 20%, the researchers reported in the Jan. 5 issue of the New England Journal of Medicine.

"We're really disappointed by the results," study co-author Peter Leone, MD, of the University of North Carolina in Chapel Hill, told MedPage Today. But, he said, "it's the reason we do clinical trials."

Action Points

· In prior studies, this herpes simplex vaccine markedly reduced the risk of genital herpes disease in women in so-called serodiscordant couples, in which one partner had the virus and other did not.

· However, in this study of women who were seronegative for HSV-1 and HSV-2 and representative of the general population, the vaccine had some efficacy in preventing HSV-1 genital disease and infection but not in preventing HSV-2 disease or infection.

The vaccine showed some efficacy against herpes simplex-1 (HSV-1), but not against herpes simplex-2 (HSV-2), the researchers reported.

Since both viruses are common and clinically indistinguishable, Leone said, the vaccine probably would have a limited public health benefit and won't be pursued.

He said researchers probably will need to take a "different type of vaccine approach" in order to find something that works against both viruses.

In general, HSV-2 is regarded as more worrisome since it tends to recur more than HSV-1 and also is associated with an increased risk of acquiring HIV.

In the two earlier clinical trials, among discordant couples, the vaccine showed efficacy of 73% and 74% against genital disease (caused by either virus) among women who did not have antibodies against HSV-1 or HSV-2. There was no effect in men.

For this study, the researchers enrolled 8,323 women, ages 18 to 30, who did not have antibodies to either virus. They were randomly assigned to the herpes vaccine or to a hepatitis A vaccine.

The primary endpoint was occurrence of genital herpes disease due to either HSV-1 or HSV-2.

Analysis showed:

· Overall, the vaccine was just 20% efficacious in preventing genital herpes disease

· It was 58% efficacious against disease caused by HSV-1 but had no effect against HSV-2 disease

· Overall, the vaccine protected against infection with an efficacy of 22%, but that was driven by a 35% efficacy against HSV-1 infection. There was no effect against HSV-2 infection

The researchers noted that the findings are "puzzling in view of the previous two studies involving discordant couples" -- both of which showed efficacy against HSV-2.

Leone said the difference might be a function of exposure among women in those trials, since by definition their male partners were infected with one of the two viruses.

Such exposure might have led to a cellular immune response even though it was not enough to cause the women to develop antibodies, he said.

The vaccine led to a robust antibody response against HSV-2, he noted, but those very antibodies "may have blunted any protective effect of the cellular immune response."

Interestingly, there were only two cases of HSV-1 disease in those two studies (one in each), the researchers noted, so that it was impossible to evaluate efficacy against that virus.

The study was supported by the National Institute of Allergy and Infectious Diseases and by GlaxoSmithKline. Belshe reported financial links with Vivaldi Biosciences, GlaxoSmithKline, MedImmune, and Merck. Leone reported financial links with GlaxoSmithKline, Novartis, Abbott Diagnostics, and Genocea. Several other authors also reported financial links with industry.

Primary source: New England Journal of Medicine

Source reference:

Belshe RB, et al "Efficacy results of a trial of a herpes simplex vaccine" N Engl J Med 2012; 366: 34-43.

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