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WASHINGTON -- Patients with genital herpes infection had significant reductions in viral shedding following treatment with an investigational vaccine, results of a phase II trial showed.

Reductions in viral shedding ranged as high as 55% in patients who received the highest dose combination of herpes simplex virus-2 antigen and matrix M-2 adjuvant. Lesion counts declined by as much as 69% across the range of doses in the 310-patient study.

Antiviral activity persisted during 6 months of post-treatment follow-up, and adverse events have generally been mild-moderate, , of the Center for Clinical Studies in Houston, reported at the American Academy of Dermatology meeting.

"GEN-003 [vaccine] demonstrated a profound and durable effect on viral shedding and lesion rates," Nawas said. "The best dose combination was 60 micrograms of protein and 75 micrograms of adjuvant. The vaccine was safe and well tolerated."

If approved, the vaccine would be the first therapeutic vaccine (as opposed to prophylactic) for any infectious disease, she added.

Despite decades of research, genital herpes remains an incurable sexually transmitted infection, affecting an estimated 500 million people worldwide, including one in six people in the U.S. Reactivation of latent virus leads to eruption of painful genital lesions. Viral shedding can occur asymptomatically, as well as during symptomatic reactivation, and lead to disease transmission.

Standard treatment with nucleoside analogs reduces the duration of primary disease, and the duration and frequency of secondary outbreaks, but does not eliminate viral shedding, Nawas said.

Goals of an effective therapeutic vaccine would cure the infection (ideal), decrease recurrence, and decrease viral shedding to reduce the risk of disease transmission. An effective vaccine would elicit a robust humoral (B-cell) and cellular (T-cell) response, which is important in the case of HSV-2, an intracellular pathogen.

GEN-003 consists of the immunogenic proteins gD2 (a surface glycoprotein) and ICP4 (an HSV transcription factor) and the proprietary adjuvant to augment the immune response. A phase I/IIa trial of the vaccine in 143 HSV2-infected patients showed reduced shedding and lesion counts and durable humoral and cellular responses lasting for a year.

Nawas reported 6-month findings from a phase II trial to determine the vaccine's effect on viral shedding. Secondary objectives included lesion counts, time to recurrence, and the proportion of patients who were lesion free at 6 and 12 months.

Investigators randomized adults with symptomatic genital herpes to receive three doses of placebo versus 30 or 60 µg of antigen combined with 25, 50, or 75 µg of adjuvant. Results at 6 months showed that all patients who received active vaccine had significant reductions in HSV-2 shedding compared with placebo.

The data showed that the 60-µg protein dose was more effective than the 30-µg protein dose (P<0.0001, P<0.05, respectively, versus placebo). The best combination was 60 µg/75 µg, which reduced viral shedding by 55%. Lesion counts across the range of vaccine combinations decreased by 43% to 69% from baseline, and all combinations significantly reduced lesion count except the 30 µg/25 µg combination.

"We even saw reductions in the lesion count in the placebo group," Nawas said. "Our theory is that maybe the patients were expecting a benefit and told us the lesions were reduced because of that."

Viral shedding did not decrease in the placebo group, she added.

In general, local and systemic adverse events were dose-related and were most common with the first dose of vaccine. Systemic adverse events consisted primarily of myalgia and fatigue, and local adverse events consisted of pain and swelling at the injection site. One or two patients discontinued because of adverse events in all treatment groups (including placebo) with the exception of the lowest vaccine combination.

Nawas said 12-month results from the trial will be reported later this year.

During the discussion that followed the presentation, an unidentified member of the audience asked about the quality of evidence linking reductions in viral shedding to a reduced risk of disease transmission. The senior investigator in the trial, , also of the Houston clinical research center, responded that the issue was resolved more than a decade ago when clinical trials of valacyclovir (Valtrex) demonstrated a direct correlation between reduced viral shedding and lower rates of infection transmission.

In response to another question, Nawas said the vaccine's potential for prophylactic use might also be evaluated at some point.

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