ASM Microbe

ASM Microbe

Perspective from Lynn W. Enquist, PhD
June 20, 2016
3 min read

More data support efficacy of GEN-003 therapeutic vaccine for HSV-2

Perspective from Lynn W. Enquist, PhD
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BOSTON — Three doses of a novel therapeutic DNA vaccine for genital herpes reduced viral shedding and genital lesion formation, according to results from a phase 2 clinical trial. The effect of the regimen appears to last for up to 1 year, researchers reported.

“Genital herpes is an important clinical disease that affects approximately 15% of the adult population in the United States, and more in minority populations,” Kenneth H. Fife, MD, PhD, investigator and professor of medicine at Indiana University, said during a media briefing at ASM Microbe 2016. “It’s also a worldwide epidemic. It’s the most common cause of genital ulcer disease throughout the world.”

Kenneth Fife

Kenneth H. Fife

Fife said that while current antiviral therapies do a “reasonable job” managing symptoms of herpes simplex virus-2 (HSV-2), these drugs are unable to eliminate viral shedding — a key factor in the transmission of the virus. Moreover, he said, these therapies have not been shown to reduce the propensity of HSV-2 to facilitate HIV transmission.

“Improved therapies for genital herpes are needed,” Fife said.

In the study, more than 300 participants with a history of chronic, recurrent HSV-2 received either placebo or three immunizations with GEN-003, which contains the T-cell antigen ICP4 and the B-cell antigen gD2, spaced 3 weeks apart. The vaccine was administered at either 30 µg or 60 µg and in combination with either 25 µg, 50 µg or 75 µg of the novel adjuvant Matrix-M (Novavax). Over the course of 1 year, researchers measured viral shedding, the number of visible legions and participants’ immune response against HSV-2.

According to Fife, GEN-003 reduced viral shedding by 15% to 60%, with higher doses producing the greatest and most durable responses. The change in viral shedding was seen immediately after the vaccination was given and remained “relatively constant” at 6 and 12 months, he said. The combination of 60 µg of vaccine and 50 µg or 75 µg of adjuvant appeared to be the most effective combination. GEN-003 also significantly reduced the frequency of lesion outbreaks, Fife said.

Data pertaining to participants’ immune response against HSV-2 are currently being analyzed and will be presented at a later date.

The vaccine was “relatively well-tolerated” with some adverse events, Fife said, the most common of which were local reactions such as swelling and soreness of the arm in the first few days following vaccination. Systemic reactions such as fever were less common, and the second and third doses were actually better-tolerated than the first. One or two patients per dose group discontinued treatment as a result of adverse events, but there were no serious adverse events documented in the study.

According to Fife, GEN-003 could potentially control symptoms and reduce viral shedding and lesion formation for up to 1 year in place of taking antiviral drugs on a daily basis, and widespread use of the vaccine may reduce transmission of the disease. “Another possibility would be to combine it with antiviral drugs to provide an even better overall response to control the disease,” he said.

Similar results supporting the efficacy of GEN-003 were presented this year at the American Academy of Dermatology annual meeting and the NFID’s Annual Conference on Vaccine Research. Further studies are planned, according to Fife, and will likely focus on combinations of the higher doses of vaccine and the adjuvant.

“Immunotherapy does work,” Fife told Infectious Disease News. “This is the first therapeutic vaccine that has been shown to have a significant biologic effect.” – by John Schoen


Flechtner J, et al. Abstract S6. Presented at: Annual Conference on Vaccine Research; April 18-20, 2016; Baltimore.

Nawas Z, et al. F053. Late-Breaking Research: Clinical Trials. Presented at: American Academy of Dermatology Annual Meeting; March 4-8, 2016; Washington, D.C.

Wald A, et al. Therapeutic DNA Vaccine for Genital Herpes. Presented at: ASM Microbe; June 16-21, 2016; Boston.

Disclosure: Fife is an investigator for Vical Inc.