Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age: results from a randomised, controlled, double-blind trial

Abstract

Objective: The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed.

Methods: Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus.

Results: No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants.

Conclusion: The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.

Trial registration: ClinicalTrials.gov NCT00224484.

Keywords: (S)AE; (serious) adverse event; 95% CI; 95% confidence interval; AS04; ATP; Alum; ELISA; ELISA units; EU; GMC; GSK; Genital herpes; GlaxoSmithKline; HAV; HSV; HSV vaccine; HSV-1; HSV-2; Herpes simplex virus type 1; Herpes simplex virus type 2; IU; IgG; MPL; NOCD; OD; Safety; TVC; according to protocol; aluminium hydroxide; aluminium hydroxide and 3-O-deacylated monophosphoryl lipid A adjuvant system; enzyme-linked immunosorbent assay; gD2; geometric mean concentration; hepatitis A vaccine; herpes simplex virus; herpes simplex virus type 1; herpes simplex virus type 2; herpes simplex virus type 2 glycoprotein D; immunoglobulin G; international units; monophosphoryl lipid A; new onset chronic diseases; optical density; total vaccinated cohort.