MF59 and immunogenicity of H5N1 vaccine

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http://www.journals.uchicago.edu/doi/abs/10.1086/527489

The Journal of Infectious Diseases 2008;197:667?675? 2008 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2008/19705-0009$15.00
DOI: 10.1086/527489

MAJOR ARTICLE
Effects of Adjuvants on the Safety and Immunogenicity of an Avian Influenza H5N1 Vaccine in Adults

David I. Bernstein,¹
Kathryn M. Edwards,²
Cornelia L. Dekker,³
Robert Belshe,⁴
Helen K. B. Talbot,⁵
Irene L. Graham,⁴
Diana L. Noah,⁶
Fenhua He,⁷ and
Heather Hill⁷
¹ Division of Infectious Diseases, Cincinnati Children?s Hospital Medical Center, Cincinnati, Ohio; ²Pediatric Infectious Diseases and ⁵Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; ³Pediatric Infectious Diseases, Stanford University School of Medicine, Stanford, California; ⁴Infectious Diseases and Immunology, St. Louis University, St. Louis, Missouri; ⁶Southern Research Institute, Birmingham, Alabama; ⁷EMMES, Rockville, Maryland.
Background. Influenza A H5N1 viruses pose a significant threat to human health.

Methods. We conducted a multicenter, randomized, double-blind study in 394 healthy adults. Subjects were randomly assigned to receive 2 intramuscular doses of either saline placebo; influenza A/Vietnam/1203/2004(H5N1) vaccine alone at 45, 30, or 15 μg per dose; vaccine at 15 or 7.5 μg per dose with MF59; or vaccine at 30, 15, or 7.5 μg per dose with aluminum hydroxide. Subjects were followed up for safety and blood samples were obtained to determine antibody responses.

Results. The vaccine formulations were well tolerated but local adverse effects were common; the incidence of these effects increased in a dose-dependent manner and was increased by the addition of adjuvants. The addition of MF59 increased the antibody response, whereas the addition of aluminum hydroxide did not. The highest antibody responses were seen in the group that received 15 μg of vaccine per dose with MF59, in which 63% of subjects achieved the predetermined endpoint (hemagglutination-inhibition titer 40) 28 days after the second dose, compared with 29% in the group that received the highest dose (45 μg per dose) of vaccine alone.

Conclusions. A 2-dose regimen of subvirion influenza A (H5N1) vaccine was well tolerated. The antibody responses to 15 μg of A/H5 vaccine with MF59 were higher than the responses to 45 μg of vaccine alone.

Trial registration. ClincalTrials.gov identifier: http://www.clinicaltrials.gov/ct2/sh...00280033?term= NCT00280033&rank=1NCT00280033.


Received 1 August 2007; accepted 27 September 2007; electronically published 8 February 2008.

• Potential conflicts of interest: D. I. B. receives funding for clinical studies from Medimmune, GlaxoSmith-Kline, and Sanofi. K.M.E. receives research funding from Sanofi and Medimmune, and is a consultant for PATH. C.L.D. worked for Chiron Vaccines until 1997, but currently has no relationship or holdings with them. R.B. is a consultant for Medimmune and Chiron; a speaker for Merck, Medimmune and Sanofi; and receives funding from Medimmune and Merck. Other authors report no relevant conflicts.
  Financial support: National Institutes of Health (N01 AI 25459, to D.I.B.; AI 25462, to K.M.E.; and AI 25464, to R.B.).

Reprints or correspondence: Dr. David Bernstein, 3333 Burnet Ave, ML 6014, Cincinnati, OH 45229 (david.bernstein@cchmc.org).