Safety and immunogenicity of nonadjuvanted and MF59-adjuvanted influenza A/H9N2 vaccine preparations

Clin Infect Dis. 2006 Nov 1;43(9):1135-42. doi: 10.1086/508174. Epub 2006 Sep 25.

Abstract

Background: Influenza A/H9N2 viruses can infect humans and are considered to be a pandemic threat. Effective vaccines are needed for these and other avian influenza viruses.

Methods: We performed a phase I, randomized, double-blind trial to evaluate the safety and immunogenicity of a 2-dose schedule (administered on days 0 and 28) of 4 dose levels (3.75, 7.5, 15, and 30 microg of hemagglutinin) of inactivated influenza A/chicken/Hong Kong/G9/97 (H9N2) vaccine with and without MF59 adjuvant. Vaccine safety was assessed with a diary and selected blood tests. Immunogenicity was measured using serum hemagglutination inhibition (HAI) and microneutralization (MNt) antibody assays. RESULTS. Ninety-six healthy adults (age, 18-34 years) were enrolled in the study. Arm discomfort was more common in groups that received adjuvant, but adverse effects of the vaccination were generally mild. Geometric mean serum HAI and MNt antibody titers to the influenza A/chicken/Hong Kong/G9/97 (H9N2) virus strain for all vaccine groups were similar on day 0 but were significantly higher (P<.001) on both days 28 and 56 for the MF59-adjuvanted vaccine groups than for groups given nonadjuvanted vaccine. Other measures of immunogenicity were also higher in the adjuvanted vaccine groups. HAI and MNt geometric mean titers measured after the administration of a single dose of MF59-adjuvanted vaccine were similar to those measured after 2 doses of nonadjuvanted vaccine.

Conclusions: The combination of MF59 adjuvant with a subunit vaccine was associated with improved immune responses to an influenza A/H9N2 virus. The adjuvanted vaccine was immunogenic even after a single dose, raising the possibility that a 1-dose vaccination strategy may be attainable with the use of adjuvanted vaccine.

Trial registration: ClinicalTrials.gov NCT00133471.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Adult
  • Double-Blind Method
  • Humans
  • Influenza A Virus, H9N2 Subtype / immunology*
  • Influenza Vaccines / adverse effects*
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Polysorbates / pharmacology
  • Safety
  • Squalene / immunology
  • Squalene / pharmacology

Substances

  • Adjuvants, Immunologic
  • Influenza Vaccines
  • MF59 oil emulsion
  • Polysorbates
  • Squalene

Associated data

  • ClinicalTrials.gov/NCT00133471