title: Phase I study of a herpes simplex virus type 2 (HSV-2) DNA vaccine administered to healthy, HSV-2-seronegative adults by a needle-free injection system.
abstract: We conducted a double-blind, vehicle-controlled, dose escalation safety and immunogenicity trial of a candidate herpes simplex virus type 2 (HSV-2) surface glycoprotein D2 (gD2) DNA vaccine administered by use of a needle-free device. Sixty-two healthy adults were randomized using a 4:1 vaccine-to-placebo ratio. Half of the participants were HSV-1 seronegative, and all were HSV-2 seronegative. Vaccine doses included 100 microg, 300 microg, 1,000 microg or 3,000 microg of a plasmid expressing the gD2 protein. Subjects received vaccine at 0, 4, 8, and 24 weeks. Some subjects received an additional 1,000-microg boost at 52 weeks. We found that the vaccine was safe and well tolerated, with most adverse events being local site reactions. No dose-limiting toxicities were observed. gD2-specific cytotoxic T-lymphocyte and lymphoproliferation responses were detected 2 weeks after the third vaccine injection in one of four HSV-1-seronegative, HSV-2-seronegative participants who received 3,000 microg of vaccine. A DNA-based vaccination strategy against HSV-2 appears to be safe and may generate a vaccine-specific cellular immune response, but high vaccine doses are likely needed to elicit an immune response in most vaccinees.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Cattamanchi
authors.forename: Christine M
authors.initials: CM
authors.lastname: Posavad
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.forename: Yaela
authors.initials: Y
authors.lastname: Baine
authors.forename: Jennifer
authors.initials: J
authors.lastname: Moses
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Higgins
authors.forename: Richard
authors.initials: R
authors.lastname: Ginsberg
authors.forename: Richard
authors.initials: R
authors.lastname: Ciccarelli
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
mesh_terms: D000328:Adult; D049109:Cell Proliferation; D003601:Cytotoxicity Tests, Immunologic; D004311:Double-Blind Method; D005260:Female; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007267:Injections / Q000379:methods; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D010957:Plasmids; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D022301:Herpes Simplex Virus Vaccines; D010919:Placebos; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2
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