Reproducibility of Serology Assays for Pandemic Influenza H1N1: Collaborative Study to Evaluate a Candidate WHO International Standard

Vaccine. 2012 Jan 5;30(2):210-7. doi: 10.1016/j.vaccine.2011.11.019. Epub 2011 Nov 17.

Abstract

Haemagglutination-inhibition (HI) and virus neutralisation (VN) assays are used to evaluate immunogenicity of pandemic H1N1 vaccines; however these bioassays are poorly standardised leading to inter-laboratory variation. A candidate International Standard (IS) for antibody to H1N1 pdm virus (09/194) was prepared from pooled sera of subjects who had either recovered from H1N1 pdm infection or who had been immunised with an adjuvanted subunit vaccine prepared from reassortant virus NYMC X-179A (derived from A/California/7/2009 virus). Ten laboratories from seven countries tested the candidate IS, 09/194 and a panel of human sera by HI and VN using the A/California/7/2009 virus (six laboratories) and/or the reassortant virus NYMC X-179A (ten laboratories). As expected, the inter-laboratory variability for HI and VN assay results was high. For results of antibody tests to NYMC X-179A, the % geometric coefficient of variation (%GCV) for 09/194 between laboratories was 83% for HI and 192% for VN. For tests of all sera, the median %GCV ranged from 95 to 345% for HI (80-fold variation) and 204 to 383% for VN (109-fold variation), but for the titres relative to 09/194 the median %GCV was much reduced (HI 34-231%; VN 44-214%). For tests of antibody to the A/California/7/2009 wild type virus there were similar reductions in %GCV when 09/194 was used. These results suggest that 09/194 will be of use to standardise assays of antibody to A/California/7/2009 vaccine and 09/194 has now been established by WHO as an IS for antibody to A/California/7/2009 with an assigned potency of 1300 IU per ml.

MeSH terms

  • Antibodies, Viral / blood*
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Influenza Vaccines / standards*
  • International Cooperation
  • Reference Standards
  • Reproducibility of Results
  • Serologic Tests / methods
  • Serologic Tests / standards
  • World Health Organization

Substances

  • Antibodies, Viral
  • Influenza Vaccines