A randomized clinical trial of an inactivated avian influenza A (H7N7) vaccine

PLoS One. 2012;7(12):e49704. doi: 10.1371/journal.pone.0049704. Epub 2012 Dec 11.


Background: Concern for a pandemic caused by a newly emerged avian influenza A virus has led to clinical trials with candidate vaccines as preparation for such an event. Most trials have involved vaccines for influenza A (H5N1), A (H7N7) or A (H9N2).

Objective: To evaluate dosage-related safety and immunogenicity of an inactivated influenza A (H7N7) vaccine in humans.

Design: One hundred twenty-five healthy young adults were randomized to receive two doses intramuscularly of placebo or 7.5, 15, 45 or 90 µg of HA of an inactivated subunit influenza A (H7N7) vaccine (25 per group), four weeks apart. Reactogenicity was evaluated closely for one week and for any adverse effect for six months after each dose. Serum hemagglutination-inhibiting and neutralizing antibody responses were determined four weeks after each dose and at six months.

Results: Reactogenicity evaluations indicated the vaccinations were well tolerated. Only one subject developed a ≥4-fold serum hemagglutination-inhibition (HAI) antibody response and a final titer of ≥1:40 four weeks after dose two and only five subjects developed a neutralizing antibody rise and a final titer of ≥1:40 in tests performed at a central laboratory. Four of the five were given the 45 or 90 µg HA dosage. A more sensitive HAI assay at the study site revealed a dose-response with increasing HA dosage but only 36% in the 90 µg HA group developed a ≥4-fold rise in antibody in this test and only one of these achieved a titer of ≥1:32.

Conclusion: This inactivated subunit influenza A (H7N7) vaccine was safe but poorly immunogenic in humans.

Trials registration: ClinicalTrials.gov NCT00546585.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies, Viral / blood
  • Antibody Formation / immunology
  • Birds / immunology
  • Birds / virology
  • Female
  • Humans
  • Influenza A Virus, H7N7 Subtype / immunology
  • Influenza A Virus, H7N7 Subtype / pathogenicity
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / adverse effects
  • Influenza in Birds* / immunology
  • Influenza in Birds* / prevention & control
  • Influenza, Human* / immunology
  • Influenza, Human* / prevention & control
  • Male
  • Vaccines, Inactivated / administration & dosage*
  • Vaccines, Inactivated / adverse effects


  • Antibodies, Viral
  • Influenza Vaccines
  • Vaccines, Inactivated

Associated data

  • ClinicalTrials.gov/NCT00546585