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

• Published in: The Journal of infectious diseases Vol. 198; no. 9; pp. 1309 - 1316
• Main Authors: Keitel, Wendy A., Campbell, James D., Treanor, John J., Walter, Emmanuel B., Patel, Shital M., He, Fenhua, Noah, Diana L., Hill, Heather
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.11.2008; University of Chicago Press
• Subjects: Adjuvants, Immunologic - chemistry; Adjuvants, Immunologic - pharmacology; Adolescent; Adult; Aluminum; Aluminum Hydroxide - chemistry; Aluminum Hydroxide - pharmacology; Antibodies; Biological and medical sciences; Clinical trials; Dose-Response Relationship, Immunologic; Double-Blind Method; Female; Fundamental and applied biological sciences. Psychology; H5N1 subtype influenza A virus; Hemagglutinins - adverse effects; Hemagglutinins - chemistry; Hemagglutinins - immunology; Humans; Hydroxides; Immune response; Infectious diseases; Influenza A Virus, H5N1 Subtype - immunology; Influenza Vaccines - adverse effects; Influenza Vaccines - chemistry; Influenza Vaccines - immunology; Injection sites; Male; Medical sciences; Microbiology; Middle Aged; Pandemics; Vaccination; Viruses; Infection; Immunogenicity; Microbiology; Viral disease; Phase II trial; Phase I trial; Influenza A; Inactivated strain
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/592172

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 µg of hemagglutinin (HA), with or without 600 µg of aluminum hydroxide (AlOH), or 3.75 µg of HA, with or without 300 µg 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 µg of HA, 7.7 and 5.3 for those who received 7.5 µg of HA, 8.1 and 8.5 for those who received 15 µg of HA, and 14.8 and 12 for those who received 45 µg of HA. A ⩾4-fold increase in titer was observed in 2% and 2% of subjects who received 3.75 µg of HA with or without AlOH, respectively; in 14% and 0% who received 7 µg of HA; in 14% and 13% who received 15 µg of HA; and in 33% and 25% who received 45 µg of HA. Addition of AlOH enhanced responses only for subjects who received 7.5 µg of HA, but responses in subjects who received 7.5 µg of HA without AlOH were unexpectedly low. Conclusion. Overall, a meaningful beneficial effect of AlOH adjuvant was not observed. Trial registration. ClinicalTrials.gov identifier: NCT00296634.