scholarly journals Effects of Different Doses of GEN-003, a Therapeutic Vaccine for Genital Herpes Simplex Virus-2, on Viral Shedding and Lesions: Results of a Randomized Placebo-Controlled Trial

2018 ◽  
Vol 218 (12) ◽  
pp. 1890-1899 ◽  
Author(s):  
Nicholas Van Wagoner ◽  
Kenneth Fife ◽  
Peter A Leone ◽  
David I Bernstein ◽  
Terri Warren ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Genital Herpes ◽  
Controlled Trial ◽  
Therapeutic Vaccine ◽  
Serious Adverse Events ◽  
Viral Shedding ◽  
Efficacious Vaccine ◽  
Rate Ratios ◽  
Simplex Virus

Abstract Background GEN-003 is a candidate therapeutic vaccine for genital herpes simplex virus type 2 (HSV-2). We compared virologic and clinical impact of varying GEN-003 doses. Methods Adults with symptomatic HSV-2 received placebo or GEN-003 (30 or 60 µg antigen with 25, 50, or 75 µg adjuvant). Viral shedding and lesion rates before vaccination were compared with those measured immediately after vaccination, then at weeks 29–33 and 53–57 after last dose. Results Compared with baseline shedding rates, the rate ratios for viral shedding immediately after treatment were as follows: 0.82 (95% confidence interval [CI], 0.49–1.36), 30 µg antigen/25 µg adjuvant (30/25) dose; 0.64 (95% CI, 0.45–0.92), 30/50 dose; 0.63 (95% CI, 0.37–1.10), 30/75 dose; 0.56 (95% CI, 0.36–0.88), 60/25 dose; 0.58 (95% CI, 0.38–0.89), 60/50 dose; 0.45 (95% CI, 0.16–0.79), 60/75 dose; and 0.98 (95% CI, 0.76–1.26), placebo. Lesion rate reductions by GEN-003 ranged from 31% to 69%, but lesion rates also decreased among placebo recipients (62%). Reductions in shedding and lesion rate were durable for 12 months for the 60 µg antigen plus 50 or 75 µg adjuvant groups. No serious adverse events occurred with vaccination. Conclusions The most efficacious vaccine combinations for GEN-003 were the 60 µg/50 µg and 60 µg/75 µg doses.

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

2017 ◽  
Vol 215 (6) ◽  
pp. 856-864 ◽  
Author(s):  
David I. Bernstein ◽  
Anna Wald ◽  
Terri Warren ◽  
Kenneth Fife ◽  
Stephen Tyring ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Genital Herpes ◽  
Therapeutic Vaccine ◽  
Neutralizing Antibody ◽  
Serious Adverse Events ◽  
Viral Shedding ◽  
Dose Number ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

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).

scholarly journals Effect of Resiquimod 0.01% Gel on Lesion Healing and Viral Shedding When Applied to Genital Herpes Lesions

2007 ◽  
Vol 52 (2) ◽  
pp. 477-482 ◽  
Author(s):  
Kenneth H. Fife ◽  
Tze-Chiang Meng ◽  
Daron G. Ferris ◽  
Ping Liu
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Confidence Interval ◽  
Genital Herpes ◽  
Cox Proportional Hazard Model ◽  
Proportional Hazard ◽  
Proportional Hazard Model ◽  
Viral Shedding ◽  
Cox Proportional Hazard ◽  
Simplex Virus

ABSTRACT Resiquimod, a Toll-like receptor 7/8 agonist developed as a topical treatment to decrease recurrences of anogenital herpes, induces proinflammatory cytokines that may delay lesion healing. Adults with frequently recurring anogenital herpes were randomized within 24 h of onset of a recurrence to vehicle or resiquimod 0.01% gel two times per week for 3 weeks. Subjects underwent daily lesion assessments and sampling for herpes simplex virus DNA PCR for 21 days or until investigator-determined healing of lesion(s). Eighty-two subjects with a mean age of 39 ± 10.5 years and a median of seven recurrences per year were enrolled in the study. The qualifying recurrence was positive by PCR for herpes simplex virus in 68% of subjects. No difference was observed between the vehicle (39 subjects) and resiquimod (43 subjects) groups with respect to time to healing (median of 7.0 days versus median of 6.5 days, respectively; Cox proportional hazard model ratio of 1.229; 95% confidence interval, 0.778 to 1.942; P = 0.376). The distributions of maximum severity scores for any investigator-assessed local skin signs and for subject-assessed local symptoms were similar between treatment groups (P = 0.807 and P = 0.103, respectively). For subjects with at least one positive PCR result, no difference was observed for time to cessation of viral shedding (median of 7 days versus median of 5 days for vehicle and resiquimod groups, respectively; Cox proportional hazard model ratio of 1.471; 95% confidence interval, 0.786 to 2.754; P = 0.227). Application of resiquimod 0.01% two times per week for 3 weeks did not delay the healing of genital herpes lesions or reduce acute viral shedding.

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