tetano
Editor, Senior Moderator
Preexisting human antibodies neutralize recently emerged H7N9 influenza strains
Carole J. Henry Dunand[SUP]1[/SUP], Paul E. Leon[SUP]2,[/SUP][SUP]3[/SUP], Kaval Kaur[SUP]1,[/SUP][SUP]4[/SUP], Gene S. Tan[SUP]2[/SUP], Nai-Ying Zheng[SUP]1[/SUP], Sarah Andrews[SUP]1[/SUP], Min Huang[SUP]1[/SUP], Xinyan Qu[SUP]1[/SUP], Yunping Huang[SUP]1[/SUP], Marlene Salgado-Ferrer[SUP]1[/SUP], Irvin Y. Ho[SUP]1[/SUP], William Taylor[SUP]1[/SUP], Rong Hai[SUP]2[/SUP], Jens Wrammert[SUP]5[/SUP], Rafi Ahmed[SUP]5[/SUP], Adolfo Garc?a-Sastre[SUP]2,[/SUP][SUP]6,[/SUP][SUP]7[/SUP], Peter Palese[SUP]2,[/SUP][SUP]6[/SUP], Florian Krammer[SUP]2[/SUP] and Patrick C. Wilson[SUP]1,[/SUP][SUP]4[/SUP]
[SUP]1[/SUP]Department of Medicine, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, Illinois, USA.
[SUP]2[/SUP]Department of Microbiology and
[SUP]3[/SUP]Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
[SUP]4[/SUP]Committee on Immunology, The University of Chicago, Chicago, Illinois, USA.
[SUP]5[/SUP]Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
[SUP]6[/SUP]Department of Medicine and
[SUP]7[/SUP]Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Address correspondence to: Patrick C. Wilson, The University of Chicago, BSLC/Jules F. Knapp Building, 924 East 57th street, R414, Chicago, Illinois 60637, USA. Phone: 773.702.9009; E-mail: wilsonp@uchicago.edu. Or to: Florian Krammer, Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. Phone: 212.241.7318; E-mail: florian.krammer@mssm.edu.
Authorship note: Patrick C. Wilson and Florian Krammer contributed equally to this work.
Published February 17, 2015
Submitted: July 21, 2014; Accepted: January 6, 2015.
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.
http://www.jci.org/articles/view/74374
Carole J. Henry Dunand[SUP]1[/SUP], Paul E. Leon[SUP]2,[/SUP][SUP]3[/SUP], Kaval Kaur[SUP]1,[/SUP][SUP]4[/SUP], Gene S. Tan[SUP]2[/SUP], Nai-Ying Zheng[SUP]1[/SUP], Sarah Andrews[SUP]1[/SUP], Min Huang[SUP]1[/SUP], Xinyan Qu[SUP]1[/SUP], Yunping Huang[SUP]1[/SUP], Marlene Salgado-Ferrer[SUP]1[/SUP], Irvin Y. Ho[SUP]1[/SUP], William Taylor[SUP]1[/SUP], Rong Hai[SUP]2[/SUP], Jens Wrammert[SUP]5[/SUP], Rafi Ahmed[SUP]5[/SUP], Adolfo Garc?a-Sastre[SUP]2,[/SUP][SUP]6,[/SUP][SUP]7[/SUP], Peter Palese[SUP]2,[/SUP][SUP]6[/SUP], Florian Krammer[SUP]2[/SUP] and Patrick C. Wilson[SUP]1,[/SUP][SUP]4[/SUP]
[SUP]1[/SUP]Department of Medicine, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, Illinois, USA.
[SUP]2[/SUP]Department of Microbiology and
[SUP]3[/SUP]Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
[SUP]4[/SUP]Committee on Immunology, The University of Chicago, Chicago, Illinois, USA.
[SUP]5[/SUP]Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
[SUP]6[/SUP]Department of Medicine and
[SUP]7[/SUP]Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Address correspondence to: Patrick C. Wilson, The University of Chicago, BSLC/Jules F. Knapp Building, 924 East 57th street, R414, Chicago, Illinois 60637, USA. Phone: 773.702.9009; E-mail: wilsonp@uchicago.edu. Or to: Florian Krammer, Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. Phone: 212.241.7318; E-mail: florian.krammer@mssm.edu.
Authorship note: Patrick C. Wilson and Florian Krammer contributed equally to this work.
Published February 17, 2015
Submitted: July 21, 2014; Accepted: January 6, 2015.
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.
http://www.jci.org/articles/view/74374