Effect of aluminum hydroxide adjuvant on the immunogenicity of the 2009 pandemic influenza A/H1N1 vaccine: multi-level modeling of data with repeated measures.

OBJECTIVE To evaluate the effect of the aluminum hydroxide (Al-OH) adjuvant on the 2009 pandemic influenza A/H1N1 (pH1N1) vaccine. METHODS In a multicenter, double-blind, randomized, placebo-controlled trial, participants received two doses of split-virion formulation containing 15 μg hemagglutinin antigen, with or without aluminum hydroxide (Al-OH). We classified the participants into six age categories (>61 years, 41-60 years, 19-40 years, 13-18 years, 8-12 years, and 3-7 years) and obtained four blood samples from each participant on days 0, 21, 35, and 42 following the first dose of immunization. We assessed vaccine immunogenicity by measuring the geometric mean titer (GMT) of hemagglutination inhibiting antibody. We used a two-level model to evaluate the fixed effect of aluminum Al-OH and other factors, accounting for repeated measures. RESULTS The predictions of repeated measurement on GMTs of formulations with or without Al-OH, were 80.35 and 112.72, respectively. Al-OH significantly reduced immunogenicity after controlling for time post immunization, age-group and gender. CONCLUSION The Al-OH adjuvant does not increase but actually reduces the immunogenicity of the split-virion pH1N1 vaccine.