Novel Vaccine Improves Shedding and Lesion Rates in HSV-2

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GEN-003, a novel therapeutic vaccine for HSV-2 currently in clinical development, was shown to have an acceptable safety profile. <i>Photo Credit: CDC/Joe Miller.</i>
GEN-003, a novel therapeutic vaccine for HSV-2 currently in clinical development, was shown to have an acceptable safety profile. Photo Credit: CDC/Joe Miller.

In a randomized phase 1/2a trial reported in the Journal of Infectious Disease, researchers from several US universities found that a novel vaccine for genital herpes simplex virus type 2 (HSV-2) infection improved viral shedding and lesion rates.1

While the current treatment approach of suppressive therapy prevents recurrences in many cases, it is less effective in reducing viral shedding and transmission.2,3 “Transmission occurs largely from asymptomatic genital tract virus shedding, making this a key target for a therapeutic HSV vaccine,” the researchers wrote.

A preclinical study published in 2013 investigated the use of GEN-003, a candidate vaccine consisting of 2 HSV-2 antigens — a transmembrane deletion mutant of glycoprotein D (gD2ΔTMR) and a fragment of infected cell protein 4 (ICP4.2) — plus a Matrix-M2 adjuvant.4 The results showed that GEN-003 was effective in guinea pigs and elicited a T cell response in mice.

The new investigation used a double-blind, placebo-controlled, dose-escalation design (ClinicalTrials.gov identifier: NCT01667341) to test the safety and efficacy of GEN-003 in 134 human participants across 7 sites. Healthy adults with 3 to 9 yearly recurrences of genital herpes who were not taking antiviral suppressive therapy were assigned to 1 of 3 conditions: the complete GEN-003; antigens only (without the adjuvant); or placebo (saline).

The analyses revealed the following results:

  • For safety, which was the primary end point of the trial, no serious adverse events were reported;
  • Genital viral shedding rates decreased immediately after GEN-003 dosing with 30 µg (from 13.4% to 6.4%, P <.001) and 100 µg (from 15.0% to 10.3%, P <.001);
  • Lesion rates decreased immediately after GEN-003 dosing at 30 µg, from 9.7% to 5.0% (relative risk [RR] = 0.52, P <.01), and 100 µg, from 6.8% to 3.7% (RR = 0.53, P =.009); and
  • Antigen binding, neutralizing antibody, and T cell responses increased after GEN-003 dosing, and these responses increased with the addition of Matrix-M2 at each dosing level

Taken together, these findings demonstrated that immunotherapy with GEN-003 to “have an acceptable safety profile, reduce viral shedding, reduce the frequency of genital lesions and boost the humoral and cellular immune responses to HSV-2,” the researchers concluded. “The optimal dose of the proteins and adjuvant, and the durability of the effect, will require further study.”

References

  1. Bernstein DI, Wald A, Warren T, et al. Therapeutic vaccine for genital herpes simplex virus-2 infection: findings from a randomized trial [published online January 30, 2017].  J Infect Dis. doi:10.1093/infdis/jix004
  2. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137.
  3. Corey L, Wald A, Patel R, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350:11-20. doi:10.1056/NEJMoa035144
  4. Skoberne M, Cardin R, Lee A, et al. An adjuvanted herpes simplex virus 2 subunit vaccine elicits a T cell response in mice and is an effective therapeutic vaccine in Guinea pigs. J Virol. 2013;87:3930-3942. doi:10.1128/JVI.02745-12
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