David I Bernstein1, Anna Wald2, Terri Warren3, Kenneth Fife4, Stephen Tyring5, Patricia Lee5, Nick Van Wagoner6, Amalia Magaret2, Jessica B Flechtner7, Sybil Tasker7, Jason Chan7, Amy Morris8, Seth Hetherington7. 1. Cincinnati Children's Hospital Medical Center, University of Cincinnati, Ohio, USA. 2. Vaccine and Fred Hutchinson Cancer Research Center, University of Washington, Seattle, USA. 3. Westover Heights Clinic, Portland, Oregon, USA. 4. Department of Medicine, Indiana University, Indianapolis, USA. 5. University of Texas Health Science Center and Center for Clinical Studies, Houston, Texas, USA. 6. Division of Infectious Diseases, University of Alabama at Birmingham, USA. 7. Genocea Biosciences, Cambridge, Massachusetts, USA. 8. IND 2 Results, Atlanta, Georgia, USA.
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).
RCT Entities:
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).
Authors: Chaya D Patel; Sean A Taylor; Jesse Mehrbach; Sita Awasthi; Harvey M Friedman; David A Leib Journal: J Virol Date: 2020-05-18 Impact factor: 5.103
Authors: Nicholas Van Wagoner; Kenneth Fife; Peter A Leone; David I Bernstein; Terri Warren; Lori Panther; Richard M Novak; Richard Beigi; John Kriesel; Stephen Tyring; William Koltun; Gregg Lucksinger; Amy Morris; Bin Zhang; Lisa K McNeil; Sybil Tasker; Seth Hetherington; Anna Wald Journal: J Infect Dis Date: 2018-11-05 Impact factor: 5.226
Authors: Emily S Ford; Anton M Sholukh; RuthMabel Boytz; Savanna S Carmack; Alexis Klock; Khamsone Phasouk; Danica Shao; Raabya Rossenkhan; Paul T Edlefsen; Tao Peng; Christine Johnston; Anna Wald; Jia Zhu; Lawrence Corey Journal: J Clin Invest Date: 2021-05-03 Impact factor: 14.808