Immunogenicity of HBV vaccine during stated shelf-life.

Thiomersal has been used as preservative in multi-dose vials of hepatitis B vaccine (Engerix-B). Due to safety concerns, thiomersal was replaced with 2-phenoxyethanol (2PE) as preservative in multi-dose vials. The potency of 2PE preserved hepatitis B vaccine multiple use vials was measured over the shelf-life in terms of immunogenicity, reactogenicity and safety. This single-blind, randomized study was conducted with the assistance of employees of GlaxoSmithKline Biologicals, makers of the Engerix-B vaccine. Four hundred twenty subjects aged > or =18 years were randomized to receive three doses (0, 1, 6 months) of 2PE preserved hepatitis B vaccine kept on the shelf <12 months (2PE New group), 2PE preserved hepatitis B vaccine kept on the shelf >18 months (2PE Old group), or thiomersal preserved hepatitis B vaccine [HBV(Thio) group]. Anti-HBs was measured by GlaxoSmithKline Biologicals post-vaccination; the reactogenicity and safety of the vaccines were assessed. Protective anti-HBs levels (> or =10 mIU/ml) were measured one month after dose 3. The results showed protective levels in 86.8% (2PE New), 89% (2PE Old) and 95.3% [HBV(Thio)]. There was no difference detected between the 2PE New and 2PE Old groups in terms of anti-HBs seroprotection rates and geometric mean concentrations one month after dose 3. However, both 2PE groups had significantly lower seroprotection rates than the HBV(Thio) group and the number of non-responders was higher in the 2PE groups than in the Thio group. A antibody response rates over time were similar between the 2PE New and Old groups. The reactogenicity profiles were acceptable and the ranges were similar for each group. The shelf-life of the vaccines had no impact on immunogenicity or reactogenicity and 2PE preserved hepatitis B vaccine can be considered stable over time.