title: Glycoprotein-D-adjuvant vaccine to prevent genital herpes.
abstract: BACKGROUND
  An effective prophylactic vaccine would help control the spread of genital herpes.
  
  
  METHODS
  We conducted two double-blind, randomized trials of a herpes simplex virus type 2 (HSV-2) glycoprotein-D-subunit vaccine with alum and 3-O-deacylated-monophosphoryl lipid A in subjects whose regular sexual partners had a history of genital herpes. In Study 1, subjects were seronegative for herpes simplex virus type 1 (HSV-1) and HSV-2; in Study 2, subjects were of any HSV serologic status. At months 0, 1, and 6, subjects received either vaccine or a control injection and were evaluated for 19 months. The primary end point was the occurrence of genital herpes disease in all subjects in Study 1 and in HSV-2-seronegative female subjects in Study 2.
  
  
  RESULTS
  A total of 847 subjects who were seronegative for both HSV-1 and HSV-2 (268 of them women, in Study 1) and 1867 subjects who were seronegative for HSV-2 (710 of them women, in Study 2) underwent randomization and received injections. Vaccination was well tolerated and elicited humoral and cellular responses. Overall, the efficacy of the vaccine was 38 percent in Study 1 (95 percent confidence interval, -18 to 68 percent; 15 cases occurred in the vaccine group and 24 in the control group), and efficacy in female subjects was 42 percent in Study 2 (95 percent confidence interval, -31 to 74 percent; 9 cases occurred in the vaccine group and 16 in the control group). In both studies, further analysis showed that the vaccine was efficacious in women who were seronegative for both HSV-1 and HSV-2: efficacy in Study 1 was 73 percent (95 percent confidence interval, 19 to 91 percent; P=0.01), and efficacy in Study 2 was 74 percent (95 percent confidence interval, 9 to 93 percent; P=0.02). It was not efficacious in women who were seropositive for HSV-1 and seronegative for HSV-2 at base line or in men.
  
  
  CONCLUSIONS
  These studies suggest that the glycoprotein D vaccine has efficacy against genital herpes in women who are seronegative for both HSV-1 and HSV-2 at base line but not in those who are seropositive for HSV-1 and seronegative for HSV-2. It had no efficacy in men, regardless of their HSV serologic status.
authors.affiliation: Department of Pediatrics and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston 77555-0351, USA. l.stanberry@utmb.edu
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Stanberry
authors.forename: Spotswood L
authors.initials: SL
authors.lastname: Spruance
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Cunningham
authors.forename: David I
authors.initials: DI
authors.lastname: Bernstein
authors.forename: Adrian
authors.initials: A
authors.lastname: Mindel
authors.forename: Stephen
authors.initials: S
authors.lastname: Sacks
authors.forename: Stephen
authors.initials: S
authors.lastname: Tyring
authors.forename: Fred Y
authors.initials: FY
authors.lastname: Aoki
authors.forename: Moncef
authors.initials: M
authors.lastname: Slaoui
authors.forename: Martine
authors.initials: M
authors.lastname: Denis
authors.forename: Pierre
authors.initials: P
authors.lastname: Vandepapeliere
authors.forename: Gary
authors.initials: G
authors.lastname: Dubin
mesh_terms: D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006558:Herpes Genitalis / Q000453:epidemiology / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines / Q000009:adverse effects / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000302:isolation & purification; D018258:Herpesvirus 2, Human / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D014759:Viral Envelope Proteins
chemical_list: D000276:Adjuvants, Immunologic; D022301:Herpes Simplex Virus Vaccines; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2