Extent of antigenic cross-reactivity among highly pathogenic H5N1 influenza viruses

Mariette F Ducatez1, Zhipeng Cai, Malik Peiris

  • 1Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA.

Insights

Highly pathogenic H5N1 avian influenza viruses have evolved, necessitating new diagnostic tools. Ancestral strain A demonstrated the broadest reactivity, making it the best candidate for detecting diverse H5N1 strains.

Area of Science:

  • Virology
  • Immunology
  • Epidemiology

Background:

  • Highly pathogenic H5N1 avian influenza viruses emerged in 1996 and have since evolved significantly.
  • The extensive evolution of H5N1 strains prevents the use of a single strain for effective prepandemic vaccines or diagnostic reagents.

Purpose of the Study:

  • To identify H5N1 strains that can serve as effective cross-reactive diagnostic reagents.
  • To evaluate the suitability of different H5N1 clades and computationally designed ancestral strains for broad H5N1 detection.

Main Methods:

  • Compared the cross-reactivity of 27 H5N1 viruses (clades 0, 1, 2.1, 2.2, 2.3, 4) and four computationally designed ancestral strains.
  • Utilized hemagglutination inhibition (HI) and microneutralization (MN) assays to assess viral cross-reactivity.
  • Employed antigenic cartography for data analysis.

Main Results:

  • Antigenic cartographs generated from HI titers with chicken red blood cells were comparable to those from MN titers.
  • HI assays using horse red blood cells reduced antigenic distances, suggesting it as a preferred method for H5N1 diagnostics.
  • Clade 2.2 antigens showed broad antibody detection capabilities, while ancestral strain A exhibited the widest reactivity pattern among all tested strains.

Conclusions:

  • Ancestral strain A is the most promising candidate for a broad-spectrum diagnostic reagent for H5N1 avian influenza.
  • Hemagglutination inhibition with horse red blood cells is recommended as the assay of choice for H5N1 diagnostics due to its ability to discern antigenic relationships.
  • The findings support the development of more effective H5N1 diagnostic tools capable of detecting diverse and evolving viral strains.