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

J Infect Dis. 2008 Nov 1;198(9):1309-16. doi: 10.1086/592172.

Abstract

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 microg of hemagglutinin (HA), with or without 600 microg of aluminum hydroxide (AlOH), or 3.75 microg of HA, with or without 300 microg 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 microg of HA, 7.7 and 5.3 for those who received 7.5 microg of HA, 8.1 and 8.5 for those who received 15 microg of HA, and 14.8 and 12 for those who received 45 microg of HA. A > or =4-fold increase in titer was observed in 2% and 2% of subjects who received 3.75 microg of HA with or without AlOH, respectively; in 14% and 0% who received 7 microg of HA; in 14% and 13% who received 15 microg of HA; and in 33% and 25% who received 45 microg of HA. Addition of AlOH enhanced responses only for subjects who received 7.5 microg of HA, but responses in subjects who received 7.5 microg 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 .

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology*
  • Adolescent
  • Adult
  • Aluminum Hydroxide / chemistry
  • Aluminum Hydroxide / pharmacology*
  • Dose-Response Relationship, Immunologic
  • Double-Blind Method
  • Female
  • Hemagglutinins / adverse effects
  • Hemagglutinins / chemistry
  • Hemagglutinins / immunology
  • Humans
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / adverse effects
  • Influenza Vaccines / chemistry
  • Influenza Vaccines / immunology*
  • Male
  • Middle Aged

Substances

  • Adjuvants, Immunologic
  • Hemagglutinins
  • Influenza Vaccines
  • Aluminum Hydroxide

Associated data

  • ClinicalTrials.gov/NCT00296634