Preexisting human antibodies neutralize recently emerged H7N9 influenza strains
Carole J. Henry Dunand, … , Florian Krammer, Patrick C. Wilson
Carole J. Henry Dunand, … , Florian Krammer, Patrick C. Wilson
Published February 17, 2015
Citation Information: J Clin Invest. 2015;125(3):1255-1268. https://doi.org/10.1172/JCI74374.
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Research Article Immunology

Preexisting human antibodies neutralize recently emerged H7N9 influenza strains

Abstract

The emergence and seasonal persistence of pathogenic H7N9 influenza viruses in China have raised concerns about the pandemic potential of this strain, which, if realized, would have a substantial effect on global health and economies. H7N9 viruses are able to bind to human sialic acid receptors and are also able to develop resistance to neuraminidase inhibitors without a loss in fitness. It is not clear whether prior exposure to circulating human influenza viruses or influenza vaccination confers immunity to H7N9 strains. Here, we demonstrate that 3 of 83 H3 HA-reactive monoclonal antibodies generated by individuals that had previously undergone influenza A virus vaccination were able to neutralize H7N9 viruses and protect mice against homologous challenge. The H7N9-neutralizing antibodies bound to the HA stalk domain but exhibited a difference in their breadth of reactivity to different H7 influenza subtypes. Mapping viral escape mutations suggested that these antibodies bind at least two different epitopes on the stalk region. Together, these results indicate that these broadly neutralizing antibodies may contribute to the development of therapies against H7N9 strains and may also be effective against pathogenic H7 strains that emerge in the future.

Authors

Carole J. Henry Dunand, Paul E. Leon, Kaval Kaur, Gene S. Tan, Nai-Ying Zheng, Sarah Andrews, Min Huang, Xinyan Qu, Yunping Huang, Marlene Salgado-Ferrer, Irvin Y. Ho, William Taylor, Rong Hai, Jens Wrammert, Rafi Ahmed, Adolfo García-Sastre, Peter Palese, Florian Krammer, Patrick C. Wilson

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Figure 1

Identification of H3N2-specific antibodies cross-reacting with the HA of H7N9 strains.

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Identification of H3N2-specific antibodies cross-reacting with the HA of...
(A) The binding of 83 H3N2-reactive antibodies to a panel of H3N2 and H7 recombinant HA proteins was assessed using an antibody microarray. Median triplicate fluorescence ratios were used. The minimum and maximum values for each HA were used to normalize data to reflect relative binding of each antibody. The data shown are representative of 2 independent experiments. (B) Percentage of group 2 cross-reactive IgG memory cells in 13 vaccinated individuals using an ELISPOT assay. The frequency of H3N2 HA-specific IgG memory cells binding to H7 HA stalk domain was assessed using H7 stalk/H4 head chimeric HA (H4 head HA and H7 head HA were used as a control). Each symbol represents one individual. The median value (percentage) is represented in red. (C) In vitro microneutralization assay using A/Shanghai/1/2013 (H7N9) virus. The data shown are mean ± SEM of 3 to 4 replicates (2 independent experiments).