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



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.



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.



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.



NCT01667341 (funded by Genocea).
Cincinnati Children's Hospital Medical Center, University of Cincinnati, Ohio, USA.
David I
DI
Bernstein
Vaccine and Fred Hutchinson Cancer Research Center, University of Washington, Seattle, USA.
Anna
A
Wald
Westover Heights Clinic, Portland, Oregon, USA.
Terri
T
Warren
Department of Medicine, Indiana University, Indianapolis, USA.
Kenneth
K
Fife
University of Texas Health Science Center and Center for Clinical Studies, Houston, Texas, USA.
Stephen
S
Tyring
University of Texas Health Science Center and Center for Clinical Studies, Houston, Texas, USA.
Patricia
P
Lee
Division of Infectious Diseases, University of Alabama at Birmingham, USA.
Nick
N
Van Wagoner
Vaccine and Fred Hutchinson Cancer Research Center, University of Washington, Seattle, USA.
Amalia
A
Magaret
Genocea Biosciences, Cambridge, Massachusetts, USA.
Jessica B
JB
Flechtner
Genocea Biosciences, Cambridge, Massachusetts, USA.
Sybil
S
Tasker
Genocea Biosciences, Cambridge, Massachusetts, USA.
Jason
J
Chan
IND 2 Results, Atlanta, Georgia, USA.
Amy
A
Morris
Genocea Biosciences, Cambridge, Massachusetts, USA.
Seth
S
Hetherington
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D017201:Virus Shedding; D055815:Young Adult
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D014765:Viral Vaccines
GEN-003; Genital herpes; herpes simplex virus type 2 infection; therapeutic vaccine; immunotherapy