Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape
Author(s)
Type
Journal Article
Abstract
H9N2 avian influenza virus is a major cause of poultry production loss across Asia leading to the wide use
of vaccines. Efficacy of vaccines is often compromised due to the rapid emergence of antigenic variants.
To improve the effectiveness of vaccines in the field, a better understanding of the antigenic epitopes
of the major antigen, hemagglutinin, is required. To address this, a panel of nine monoclonal antibodies
were generated against a contemporary Pakistani H9N2 isolate, which represents a major Asian H9N2
viral lineage. Antibodies were characterized in detail and used to select a total of 26 unique ‘escape’
mutants with substitutions across nine different amino acid residues in hemagglutinin including seven
that have not been described as antigenic determinants for H9N2 viruses before. Competition assays
and structural mapping revealed two novel, discrete antigenic sites “H9-A” and “H9-B”. Additionally,
a second subset of escape mutants contained amino acid deletions within the hemagglutinin receptor
binding site. This constitutes a novel method of escape for group 1 hemagglutinins and could represent
an alternative means for H9N2 viruses to overcome vaccine induced immunity. These results will guide
surveillance efforts for arising antigenic variants as well as evidence based vaccine seed selection and
vaccine design.
of vaccines. Efficacy of vaccines is often compromised due to the rapid emergence of antigenic variants.
To improve the effectiveness of vaccines in the field, a better understanding of the antigenic epitopes
of the major antigen, hemagglutinin, is required. To address this, a panel of nine monoclonal antibodies
were generated against a contemporary Pakistani H9N2 isolate, which represents a major Asian H9N2
viral lineage. Antibodies were characterized in detail and used to select a total of 26 unique ‘escape’
mutants with substitutions across nine different amino acid residues in hemagglutinin including seven
that have not been described as antigenic determinants for H9N2 viruses before. Competition assays
and structural mapping revealed two novel, discrete antigenic sites “H9-A” and “H9-B”. Additionally,
a second subset of escape mutants contained amino acid deletions within the hemagglutinin receptor
binding site. This constitutes a novel method of escape for group 1 hemagglutinins and could represent
an alternative means for H9N2 viruses to overcome vaccine induced immunity. These results will guide
surveillance efforts for arising antigenic variants as well as evidence based vaccine seed selection and
vaccine design.
Date Issued
2016-01-07
Date Acceptance
2015-11-23
Citation
Scientific Reports, 2016, 6
ISSN
2045-2322
Publisher
Nature Publishing Group
Journal / Book Title
Scientific Reports
Volume
6
Copyright Statement
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unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
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Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
A VIRUS
PHYLOGENETIC ANALYSIS
HUMAN INFECTION
H5N1 VIRUSES
HONG-KONG
EVOLUTION
POULTRY
HEMAGGLUTININ
CHINA
ANTIBODY
Publication Status
Published
Article Number
18745