Safety and immunogenicity of whole-virus, alum-adjuvanted whole-virus, virosomal, and whole-virus intradermal influenza A/H9N2 vaccine formulations

Karl G. Nicholson*, Catherine I. Thompson, Jaco M. Klap, John M. Wood, Sally Batham, Robert W. Newman, Robert Mischler, Maria C. Zambon, Iain Stephenson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Avian influenza H9N2 viruses are considered as a pandemic threat. We assessed the safety and immunogenicity of fourteen H9N2 vaccine formulations. A randomized, phase I trial was done in 353 adults, aged 18-82 years. Subjects received two doses of A/Hong Kong/1073/99 (H9N2) whole-virus, alum-adjuvanted whole-virus, virosomal, or intradermal whole-virus vaccine at four doses (1.7, 5, 15 or 45 μg haemagglutinin). Sera were obtained before and three weeks after each vaccination (days 0, 21, and 42) for haemagglutination-inhibition (HAI) and neutralization assays. All formulations were well tolerated. Pre-vaccination sera from subjects aged below or above 40 years had baseline antibody to H9N2 in 1% and 16% of samples. Compared to intramuscular whole-virus vaccine, alum-adjuvanted vaccine was more immunogenic, intradermal vaccine was comparable, and virosomal vaccine less immunogenic. Among subjects under 40 years, two doses (45, 15, and 5 μg) of alum-adjuvanted vaccine achieved seroprotective HAI titres in 50%, 41%, and 39% respectively, and neutralization seroconversions in 83%, 82%, and 78% of recipients. Among subjects over 40 years, one dose (45, 15, and 5 μg) of alum-adjuvanted vaccine achieved seroprotective HAI titres in 50%, 25% and 0% respectively, and neutralization seroconversions in 88%, 63% and 63% of recipients. Among immunologically naive subjects under 40 years, two doses of vaccine are required and alum-adjuvanted vaccines were most immunogenic. Among immunologically primed subjects over 40 years, one dose of whole-virus or alum-adjuvanted vaccine induced immune responses; the second dose provided less additional benefit. However, no vaccine formulation satisfied all European regulatory criteria for pandemic vaccines.

Original languageEnglish
Pages (from-to)171-178
Number of pages8
JournalVaccine
Volume28
Issue number1
DOIs
Publication statusPublished - 10 Dec 2009

Bibliographical note

Funding Information:
Conflicts of interest : The unit of K.N. and I.S. has received research funding from Crucell-Berna, Hoffman LaRoche, Novartis Vaccines, Wyeth, Gilead, European Union and UK Medical Research Council and Health Technology Assessment; speaker and consultancy fees from Hoffman LaRoche, Novartis Vaccines, GlaxoSmithKline, Baxter and Biocryst Pharmaceuticals. J.K. is an employee of Crucell. R.M. was an employee of Berna at the time of the study. S.B., C.T., J.W., R.N. and M.Z. have no conflicts of interest. The Health Protection Agency has received funding for vaccine immunogenicity assessment from manufacturers of influenza vaccines including Sanofi-pasteur, Novartis, Baxter and CSL. Financial support : The funder, the UK Department of Health approved the study design, but took no part in data collection, data analysis, data interpretation, or writing of the report.

Keywords

  • Immunogenicity
  • Pandemic vaccine
  • Serology

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