Safety and immunogenicity of an inactivated influenza A/H5N1 vaccine given with or without aluminum hydroxide to healthy adults: Results of a phase I-II randomized clinical trial

Background. Dose-sparing strategies are being explored for vaccines against pandemic influenza. We evaluated the dose-sparing potential of aluminum hydroxide (AlOH) adjuvant. Methods. A total of 600 healthy subjects (age, 18-49 years) were randomized to receive 2 vaccinations 1 month apart with subvirion inactivated influenza A/H5N1 vaccine containing 7.5, 15, or 45 mu g of hemagglutinin (HA), with or without 600 mu g of aluminum hydroxide (AlOH), or 3.75 mu g of HA, with or without 300 mu g of AlOH. Serum specimens were obtained for antibody assays before and 1 month after each vaccination. Results. All formulations were safe. Injection site discomfort was more frequent in groups given vaccines with AlOH. Dose-related increases in antibody responses were noted after both vaccinations (P < .001): geometric mean titers of hemagglutination inhibition antibody in vaccines with and without AlOH, respectively, were 5.4 and 5.4 for subjects who received 3.75 mu g of HA, 7.7 and 5.3 for those who received 7.5 mu g of HA, 8.1 and 8.5 for those who received 15 mu g of HA, and 14.8 and 12 for those who received 45 mu g of HA. A >= 4-fold increase in titer was observed in 2% and 2% of subjects who received 3.75 mu g of HA with or without AlOH, respectively; in 14% and 0% who received 7 mu g of HA; in 14% and 13% who received 15 mu g of HA; and in 33% and 25% who received 45 mu g of HA. Addition of AlOH enhanced responses only for subjects who received 7.5 mu g of HA, but responses in subjects who received 7.5 mu g of HA without AlOH were unexpectedly low. Conclusion. Overall, a meaningful beneficial effect of AlOH adjuvant was not observed. Trial registration. ClinicalTrials.govidentifier: NCT00296634.