WASHINGTON – Research is honing in on the best dose for a therapeutic vaccine shown to reduce shedding of herpes simplex virus 2 in subjects with genital herpes infections, based on results presented at the annual meeting of the American Academy of Dermatology.
The vaccine could prove an alternative to antiviral therapy for infected patients.
In a phase II study of 310 HSV-2 infected adults, the subjects who received 60 mcg of recombinant HSV antigens gD and ICP4 and 75 mcg of Matrix M-2 adjuvant had the best response, which was a 58% reduction in viral shedding at 6 months, reported Dr. Zeena Nawas, a researcher at the Center for Clinical Studies in Houston.
The vaccine, GEN 003 (Genocea) is an HSV-2 protein subunit vaccine consisting of two recombinant T-cell antigens: internal fragment of the immediate early (IE) protein ICP and glycoprotein D. The vaccine had a “profound and durable” effect on viral shedding and could become “the first therapeutic vaccine for genital herpes,” Dr. Nawas said.
Previously, Dr. Nawas and her colleagues demonstrated GEN 003 was associated with significant reductions in genital lesions and viral shedding. The new phase II data indicates a best dose combination of antigen and adjuvant for a vaccine candidate for future trials.
For the dose-finding study, seven cohorts were derived from 310 adults with symptomatic genital herpes. Subjects were randomly assigned to receive 30 mcg or 60 mcg each of the recombinant HSV antigens gD and ICP4, plus 25, 50, or 75 mcg of the Matrix M-2 adjuvant; one cohort received a placebo vaccine.
At 6 months after immunization, genital HSV-2 shedding was significantly reduced compared to baseline values in all vaccine groups who received 60 mcg of HSV-2 antigens. The highest reduction at 58% (P less than .0001) was observed in group given the 60/75 mcg dose. With the exception of the group given the 30/25 mcg dose, all study groups had a reduction from baseline measures in genital lesions that ranged from 43% to 69% (P less than .0001).
In response to a question from session comoderator Dr. Andrew Blauvelt, president of the Oregon Medical Research Center, Dr. Nawas said that the placebo group did not have any reduction in viral shedding, making the reductions in viral shedding “clinically and statistically significant. If we have less shedding, that means that the risk of transmission is way less.”Data used to determine the clinically significant correlation between shedding and transmission were derived frompreviously reported dataon antiviral therapies. Few participants across the cohort reported adverse events, according to Dr. Nawas. Myalgia, fatigue, and erythema at the injection site were the most common adverse events. The details of the studyare available at ClinicalTrials.gov. The study is sponsored by Genocea Biosciences, maker of GEN-003.