Combined, concurrent, and sequential administration of seasonal influenza and MF59-adjuvanted A/H5N1 vaccines: a phase II randomized, controlled trial of immunogenicity and safety in healthy adults

J Infect Dis. 2011 Jun 15;203(12):1719-28. doi: 10.1093/infdis/jir191.

Abstract

Objective: We performed a phase II randomized, controlled, open-label, single-center study (Centros de Estudios de Infectología Pediátrica, Colombia) to examine the feasibility of combined administration of seasonal and MF59-adjuvanted A/H5N1 influenza vaccines using extemporaneous mixing or simultaneous administration.

Methods: The primary objective of the study was to assess the immunogenicity of seasonal influenza and A/H5N1 vaccines using European licensure criteria (Committee for Medicinal Products for Human Use [CHMP]); the secondary objective was to assess vaccine reactogenicity and safety.

Results: In 401 healthy 18-40-year-old subjects, both vaccines were immunogenic in all settings; the vaccine for seasonal influenza met all CHMP criteria, unaffected by coadministration of A/H5N1 vaccine in separate or mixed injections. Likewise, the immunogenicity of A/H5N1 vaccine was unaffected by seasonal influenza vaccination, with hemagglutination inhibition seroprotection rates of 28%-40% after 1 dose and 67%-80% after 2 doses, sufficient to meet CHMP criteria. Solicited local and systemic adverse events were mainly mild to moderate. No vaccine-related serious adverse events were reported during the study period.

Conclusions: These data demonstrate that seasonal and MF59-adjuvanted A/H5N1 influenza vaccines can be given as a mixed injection or by simultaneous separate injections without affecting immunogenicity or safety, supporting the feasibility of incorporating prepandemic MF59-adjuvanted A/H5N1 vaccines into seasonal influenza vaccination programs and the development of tetravalent influenza vaccines, including pandemic strains. Clinical Trials Registration. NCT00481065.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Female
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza B virus / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / adverse effects
  • Influenza Vaccines / immunology*
  • Influenza Vaccines / standards*
  • Influenza, Human / prevention & control*
  • Injections, Intramuscular
  • Male
  • Polysorbates
  • Squalene / immunology
  • Young Adult

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00481065