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. 2018 May 31;7(1):100.
doi: 10.1038/s41426-018-0100-7.

Antigenic characterization of highly pathogenic avian influenza A(H5N1) viruses with chicken and ferret antisera reveals clade-dependent variation in hemagglutination inhibition profiles

Diep Thi Nguyen  1   2   3   4 , Samuel S Shepard  5 , David Francis Burke  6 , Joyce Jones  5 , Sharmi Thor  5 , Long Van Nguyen  7 , Tho Dang Nguyen  8 , Amanda Balish  5 , Dang Nguyen Hoang  8 , Thanh Long To  7 , Munir Iqbal  9 , David E Wentworth  5 , Erica Spackman  10 , H Rogier van Doorn  11   12 , C Todd Davis  13 , Juliet E Bryant  14   15
Affiliations

Antigenic characterization of highly pathogenic avian influenza A(H5N1) viruses with chicken and ferret antisera reveals clade-dependent variation in hemagglutination inhibition profiles

Diep Thi Nguyen et al. Emerg Microbes Infect. .

Abstract

Highly pathogenic avian influenza (HPAI) A(H5N1) viruses pose a significant economic burden to the poultry industry worldwide and have pandemic potential. Poultry vaccination against HPAI A(H5N1) viruses has been an important component of HPAI control measures and has been performed in Vietnam since 2005. To systematically assess antigenic matching of current vaccines to circulating field variants, we produced a panel of chicken and ferret antisera raised against historical and contemporary Vietnamese reference viruses representing clade variants that were detected between 2001 and 2014. The antisera were used for hemagglutination inhibition (HI) assays to generate data sets for analysis by antigenic cartography, allowing for a direct comparison of results from chicken or ferret antisera. HI antigenic maps, developed with antisera from both hosts, revealed varying patterns of antigenic relationships and clustering of viruses that were dependent on the clade of viruses analyzed. Antigenic relationships between existing poultry vaccines and circulating field viruses were also aligned with in vivo protection profiles determined by previously reported vaccine challenge studies. Our results establish the feasibility and utility of HPAI A(H5N1) antigenic characterization using chicken antisera and support further experimental and modeling studies to investigate quantitative relationships between genetic variation, antigenic drift and correlates of poultry vaccine protection in vivo.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Antigenic maps of influenza A(H5N1) HA based on HI immune responses to chicken antisera.
Both vertical and horizontal axes represent antigenic distance. Grid lines represent 1 antigenic distance unit, corresponding to a 2-fold dilution in the HI assay. Different antigenic clusters are indicated with different colors. Filled circles indicate antigens, while open squares indicate antisera
Fig. 2
Fig. 2. Antigenic maps of influenza A(H5N1) HA based on HI immune responses to ferret antisera.
Both vertical and horizontal axes represent antigenic distance. Grid lines represent 1 antigenic distance unit, corresponding to a 2-fold dilution in the HI assay. Different antigenic clusters are indicated with different colors. Filled circles indicate antigens, while open squares indicate antisera
Fig. 3
Fig. 3. Map showing inferred relationships (antigenic distance units) between pairs of chicken and ferret reference antisera raised against the same viruses.
Grid lines represent 1 antigenic distance unit, corresponding to a 2-fold dilution in the HI assay. Different antigenic clusters are indicated with different colors. Filled circles indicate antigens, while open squares indicate antisera. Green arrows with dotted lines indicate chicken and ferret antisera pairs
Fig. 4
Fig. 4. Antigenic distances between vaccine and challenge viruses plotted against vaccine efficacy (percent survival), as determined by in vivo vaccine challenge experiments.
Each data point represents results from a challenge trial using 10 chickens/challenge virus and survival following intranasal inoculation with a dose of 106 TCID50. Blue diamonds, red squares and green triangles represent chickens vaccinated with Re-1, Re-5 and Re-6, respectively. The challenge viruses used are identified for each group of vaccinated chickens with color-coded text indicating strain name and clade
See this image and copyright information in PMC

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