Therapeutic Vaccine for Genital Herpes Simplex Virus-2 Infection: Findings From a Randomized Trial

Abstract

Background: Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate therapeutic vaccine containing HSV-2 gD2∆TMR and ICP4.2, and Matrix-M2 adjuvant.

Methods: Persons with genital herpes were randomized into 3 dose cohorts to receive 3 intramuscular doses 21 days apart of 10 µg, 30 µg, or 100 µg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swab specimens twice daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and at intervals after the last dose.

Results: One hundred and thirty-four persons received all 3 doses. Reactogenicity was associated with adjuvant but not with antigen dose or dose number. No serious adverse events were attributed to GEN-003. Compared with baseline, genital HSV-2 shedding rates immediately after dosing were reduced with GEN-003 (from 13.4% to 6.4% for 30 μg [P < .001] and from 15.0% to 10.3% for 100 µg [P < .001]). Lesion rates were also significantly (P < .01) reduced immediately following immunization with 30 µg or 100 µg of GEN-003. GEN-003 elicited increases in antigen binding, virus neutralizing antibody, and T-cell responses.

Conclusions: GEN-003 had an acceptable safety profile and stimulated humoral and cellular immune responses. GEN-003 at doses of 30 µg and 100 µg reduced genital HSV shedding and lesion rates.

Clinical trials registration: NCT01667341 (funded by Genocea).

Keywords: GEN-003; Genital herpes; herpes simplex virus type 2 infection; therapeutic vaccine; immunotherapy.

Figure 1.

Consolidated Standard of Reporting Trials diagram of the study. Abbreviations: AE, adverse event; IgG, immunoglobulin G.

Figure 2.

Rates of local and systemic solicited adverse events within 7 days following vaccination, by treatment assignment and dose number.

Figure 3.

Humoral immune responses following the third immunization measured on day 63, 3 weeks after the third immunization. A, Immunoglobulin G (IgG) response to glycoprotein gD2ΔTMR, a transmembrane deletion mutant of glycoprotein D. B, IgG response to infected cell protein 4 (ICP4.2). C, Neutralizing antibody (NAb) response. Abbreviations: CI, confidence interval; GMT, geometric mean titer. *P < .001, compared with placebo and compared with day 0 in the same group.

Figure 4.

Cellular immune responses measured on day 49, 1 week after the third immunization. A, Mean level of interferon γ (IFN-γ) release in response to glycoprotein D2. B, Mean level of IFN-γ release in response to infected cell protein 4 (ICP4.2). Abbreviations: CI, confidence interval; gD2, glycoprotein D2; SFU, spot-forming units. *P < .001, compared with placebo and compared with day 0 in the same group.