Therapeutic HSV-2 vaccine decreases recurrent virus shedding and recurrent genital herpes disease

Background: Genital herpes simplex virus (HSV) type 2 is a common persistent infection that frequently reactivates to cause recurrent lesions and recurrent viral shedding which is incompletely controlled by antiviral therapy. GEN-003 is a candidate therapeutic vaccine containing 2 HSV-2 proteins, gD2 and ICP4, and Matrix-M2 adjuvant (M2). Methods: HSV-2 seropositive persons with genital herpes were randomized into three dose cohorts of Gen-003 (60 mu g antigen/50 mu g M2, 60 mu g/75 mu g M2 or Placebo). Three intramuscular doses 21 days apart of GEN-003 or placebo were administered. Participants obtained genital area swabs twice-daily for HSV-2 detection and monitored genital lesions for 12 months. The rates of virus shedding and lesion rates before vaccination were compared to 3 defined periods after vaccination; Days 43-71, Month 6 and Month 12. Results: GEN-003 at a dose of 60 mu g each antigen/50 mu g M2 reduced HSV shedding immediately after dosing with a rate ratio of 0.58, compared to 0.75 for the GEN-003 6014/75 mu g M2 and 1.06 for placebo. Lesion rates, recurrence rates, and duration of recurrences were also reduced. Reactogenicity was higher with the 75 mu g M2 dose than the 50 mu g M2 dose, specifically for pain, tenderness, malaise and fatigue. Antibody and cellular immune responses were stimulated by both doses and persisted to 12 months. Conclusions: GEN-003 vaccine manufactured with a scalable process gave results similar to those observed in prior clinical trials. GEN-003 had an acceptable safety profile and stimulated both humoral and cellular immune responses. The 60 mu g antigen/50 mu g M2 provided the maximal effect on virologic and clinical measures and warrants further development. (C) 2019 Published by Elsevier Ltd.