Therapeutic Vaccine for Genital Herpes Simplex Virus-2 Infection: Findings From a Randomized Trial. (30th January 2017)

• Record Type: Journal Article
• Authors: Bernstein, David I.; Wald, Anna; Warren, Terri; Fife, Kenneth; Tyring, Stephen; Lee, Patricia; Van Wagoner, Nick; Magaret, Amalia; Flechtner, Jessica B.; Tasker, Sybil; Chan, Jason; Morris, Amy; Hetherington, Seth
• Is Part Of: Journal of infectious diseases. Volume 215:Number 6(2017:Mar. 15)
• Page Start: 856
• Page End: 864
• Publication Date: 2017-01-30
• Subjects: Genital herpes -- herpes simplex virus type 2 infection -- therapeutic vaccine -- GEN-003 -- immunotherapy.; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix004
• Languages: English
• ISSNs: 0022-1899

Abstract

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).