title: Immunogenicity and safety of different formulations of an adjuvanted glycoprotein D genital herpes vaccine in healthy adults: a double-blind randomized trial.
abstract: Herpes simplex virus (HSV) type 2 (HSV-2) is the main cause of genital and neonatal herpes and is highly prevalent worldwide. Previous phase I and II studies showed the immunogenicity and safety of the candidate prophylactic HSV-2 glycoprotein D-based subunit vaccine (gD2-AS04), containing aluminum hydroxide and 3-O-deacylated monophosphoryl lipid A (MPL) as adjuvant (AS04), in healthy adults. The primary objective of the study presented here was to compare the immunogenicity and safety of five different vaccine formulations: 3 different antigen doses [20, 40 or 80 μg of truncated glycoprotein D from HSV-2 strain (gD-2t)], different aluminum salts [AlPO₄ or Al(OH)₃], different preservatives or different volumes of vaccine (0.5 or 1 ml). One hundred and fifty healthy men and women aged 18-45 years, with negative serological markers for HSV-1 and HSV-2 infection, were vaccinated with one of 5 formulations of the gD2-AS04 candidate vaccine according to a 0-, 1-, 6-month schedule. No statistically significant difference was observed in humoral or cellular immune responses between different antigen doses or the different aluminum salts, preservatives or volumes of vaccine. The gD2-AS04 vaccine was well tolerated by study participants for the duration of the study period. Local symptoms were more frequently reported than general symptoms, with muscle stiffness and/or injection site redness being the most frequently reported. Overall, the incidence of adverse events was comparable in all groups. Based on these results the gD2-AS04 formulation, containing 20 μg of gD-2t, was selected for evaluation of prophylactic efficacy in further clinical trials.
authors: Center for Vaccinology; Ghent University and Hospital; Ghent, Belgium.
authors: Geert
authors: G
authors: Leroux-Roels
authors: Frédéric
authors: F
authors: Clément
authors: Pierre
authors: P
authors: Vandepapelière
authors: Marc
authors: M
authors: Fourneau
authors: Thomas C
authors: TC
authors: Heineman
authors: Gary
authors: G
authors: Dubin
mesh_terms: D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D064368:Healthy Volunteers; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control*; D022283:Herpesvirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D015994:Incidence; D008050:Lipid A / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008297:Male; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: C532963:ASO4 mixture; D022283:Herpesvirus Vaccines; D008050:Lipid A; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2; D000536:Aluminum Hydroxide
keywords: HSV vaccine; adjuvant; glycoprotein D herpes virus; herpes simplex virus; immunogenicity; protein subunit vaccine; safety