title: Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes.
abstract: Immunotherapy of chronic viral diseases with vaccines is an important but unproven concept. We investigated the effect of a vaccine containing recombinant glycoprotein D (gD2) of herpes simplex virus type 2 (HSV-2) on the frequency of symptomatic outbreaks in patients with genital herpes. 98 patients with documented genital herpes who reported 4-14 recurrences per year were enrolled in a double-blind, placebo-controlled trial. Subjects received injections of either 100 micrograms gD2 in alum or alum alone (placebo) at 0 and 2 months, and recurrences were documented for 1 year. The vaccine was well tolerated. gD2 recipients reported fewer recurrences per month than placebo recipients (mean 0.42 [SE 0.05] vs 0.55 [0.05]; p = 0.055), had fewer virologically confirmed recurrences per month (0.18 [0.03] vs 0.28 [0.03]; p = 0.019), and had a lower median number of recurrences for the study year (4 [range 0-17] vs 6 [0-15]; p = 0.039). Neither genital recurrence nor the placebo vaccine had any discernible effect on HSV-2-specific antibody responses, but gD2 vaccine boosted neutralising antibodies to HSV-2 fourfold and gD2-specific titres sevenfold over baseline levels. These results inspire optimism about the potential use of vaccine for the treatment of chronic, recurring viral diseases.
authors.affiliation: Medical Virology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: S E
authors.initials: SE
authors.lastname: Straus
authors.forename: L
authors.initials: L
authors.lastname: Corey
authors.forename: R L
authors.initials: RL
authors.lastname: Burke
authors.forename: B
authors.initials: B
authors.lastname: Savarese
authors.forename: G
authors.initials: G
authors.lastname: Barnum
authors.forename: P R
authors.initials: PR
authors.lastname: Krause
authors.forename: R G
authors.initials: RG
authors.lastname: Kost
authors.forename: J L
authors.initials: JL
authors.lastname: Meier
authors.forename: R
authors.initials: R
authors.lastname: Sekulovich
authors.forename: S F
authors.initials: SF
authors.lastname: Adair
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006558:Herpes Genitalis / Q000628:therapy*; D018258:Herpesvirus 2, Human / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012008:Recurrence; D016896:Treatment Outcome; D014759:Viral Envelope Proteins / Q000627:therapeutic use*
chemical_list: D000914:Antibodies, Viral; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1