25 Mar 2013

H3N2 Influenza Virus Infection Induces Broadly Reactive Hemagglutinin Stalk Antibodies in Humans and Mice (J Virol., abstract, edited)

[Source: Journal of Virology, full text: (LINK). Abstract, edited.]

H3N2 Influenza Virus Infection Induces Broadly Reactive Hemagglutinin Stalk Antibodies in Humans and Mice

Irina Marginea,b, Rong Haia, Randy A. Albrechta,c, Gerlinde Obermoserd, A. Carson Harrodd, Jacques Banchereaud, Karolina Paluckad, Adolfo GarcĂ­a-Sastrea,c,e, Peter Palesea,e, John J. Treanorf and Florian Krammera

Author Affiliations: aDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA bGraduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA cGlobal Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA dBaylor Institute for Immunology Research, Dallas, Texas, USA eDepartment of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA fDepartment of Medicine, University of Rochester Medical Center, Rochester, New York, USA

 

ABSTRACT

Broadly neutralizing antibodies directed against the conserved stalk domain of the viral hemagglutinin have attracted increasing attention in recent years. However, only a limited number of stalk antibodies directed against group 2 influenza hemagglutinins have been isolated so far. Also, little is known about the general level of induction of these antibodies by influenza virus vaccination or infection. To characterize the anti-stalk humoral response in the mouse model as well as in humans, chimeric hemagglutinin constructs previously developed in our group were employed in serological assays. Whereas influenza virus infection induced high titers of stalk-reactive antibodies, immunization with inactivated influenza virus vaccines failed to do so in the mouse model. Analysis of serum samples collected from human individuals who were infected by influenza viruses also revealed the induction of stalk-reactive antibodies. Finally, we show that the hemagglutinin stalk-directed antibodies induced in mice and humans have broad reactivity and neutralizing activity in vitro and in vivo. The results of the study point toward the existence of highly conserved epitopes in the stalk domains of group 2 hemagglutinins, which can be targeted for the development of a universal influenza virus vaccine in humans.

 

FOOTNOTES

Received 20 December 2012. Accepted 6 February 2013.

Address correspondence to Florian Krammer, florian.krammer@mssm.edu.

Published ahead of print 13 February 2013

Copyright © 2013, American Society for Microbiology. All Rights Reserved.

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