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Title: Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin

Abstract

Broadly neutralizing antibodies against highly variable pathogens have stimulated the design of vaccines and therapeutics. We report the use of diverse camelid single-domain antibodies to influenza virus hemagglutinin to generate multidomain antibodies with impressive breadth and potency. Multidomain antibody MD3606 protects mice against influenza A and B infection when administered intravenously or expressed locally from a recombinant adeno-associated virus vector. Crystal and single-particle electron microscopy structures of these antibodies with hemagglutinins from influenza A and B viruses reveal binding to highly conserved epitopes. Collectively, our findings demonstrate that multidomain antibodies targeting multiple epitopes exhibit enhanced virus cross-reactivity and potency. In combination with adeno-associated virus–mediated gene delivery, they may provide an effective strategy to prevent infection with influenza virus and other highly variable pathogens.

Authors:
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Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
INDUSTRYNIH
OSTI Identifier:
1481297
Resource Type:
Journal Article
Journal Name:
Science
Additional Journal Information:
Journal Volume: 362; Journal Issue: 6414; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Laursen, Nick S., Friesen, Robert H. E., Zhu, Xueyong, Jongeneelen, Mandy, Blokland, Sven, Vermond, Jan, van Eijgen, Alida, Tang, Chan, van Diepen, Harry, Obmolova, Galina, van der Neut Kolfschoten, Marijn, Zuijdgeest, David, Straetemans, Roel, Hoffman, Ryan M. B., Nieusma, Travis, Pallesen, Jesper, Turner, Hannah L., Bernard, Steffen M., Ward, Andrew B., Luo, Jinquan, Poon, Leo L. M., Tretiakova, Anna P., Wilson, James M., Limberis, Maria P., Vogels, Ronald, Brandenburg, Boerries, Kolkman, Joost A., and Wilson, Ian A. Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin. United States: N. p., 2018. Web. doi:10.1126/science.aaq0620.
Laursen, Nick S., Friesen, Robert H. E., Zhu, Xueyong, Jongeneelen, Mandy, Blokland, Sven, Vermond, Jan, van Eijgen, Alida, Tang, Chan, van Diepen, Harry, Obmolova, Galina, van der Neut Kolfschoten, Marijn, Zuijdgeest, David, Straetemans, Roel, Hoffman, Ryan M. B., Nieusma, Travis, Pallesen, Jesper, Turner, Hannah L., Bernard, Steffen M., Ward, Andrew B., Luo, Jinquan, Poon, Leo L. M., Tretiakova, Anna P., Wilson, James M., Limberis, Maria P., Vogels, Ronald, Brandenburg, Boerries, Kolkman, Joost A., & Wilson, Ian A. Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin. United States. doi:10.1126/science.aaq0620.
Laursen, Nick S., Friesen, Robert H. E., Zhu, Xueyong, Jongeneelen, Mandy, Blokland, Sven, Vermond, Jan, van Eijgen, Alida, Tang, Chan, van Diepen, Harry, Obmolova, Galina, van der Neut Kolfschoten, Marijn, Zuijdgeest, David, Straetemans, Roel, Hoffman, Ryan M. B., Nieusma, Travis, Pallesen, Jesper, Turner, Hannah L., Bernard, Steffen M., Ward, Andrew B., Luo, Jinquan, Poon, Leo L. M., Tretiakova, Anna P., Wilson, James M., Limberis, Maria P., Vogels, Ronald, Brandenburg, Boerries, Kolkman, Joost A., and Wilson, Ian A. Thu . "Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin". United States. doi:10.1126/science.aaq0620.
@article{osti_1481297,
title = {Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin},
author = {Laursen, Nick S. and Friesen, Robert H. E. and Zhu, Xueyong and Jongeneelen, Mandy and Blokland, Sven and Vermond, Jan and van Eijgen, Alida and Tang, Chan and van Diepen, Harry and Obmolova, Galina and van der Neut Kolfschoten, Marijn and Zuijdgeest, David and Straetemans, Roel and Hoffman, Ryan M. B. and Nieusma, Travis and Pallesen, Jesper and Turner, Hannah L. and Bernard, Steffen M. and Ward, Andrew B. and Luo, Jinquan and Poon, Leo L. M. and Tretiakova, Anna P. and Wilson, James M. and Limberis, Maria P. and Vogels, Ronald and Brandenburg, Boerries and Kolkman, Joost A. and Wilson, Ian A.},
abstractNote = {Broadly neutralizing antibodies against highly variable pathogens have stimulated the design of vaccines and therapeutics. We report the use of diverse camelid single-domain antibodies to influenza virus hemagglutinin to generate multidomain antibodies with impressive breadth and potency. Multidomain antibody MD3606 protects mice against influenza A and B infection when administered intravenously or expressed locally from a recombinant adeno-associated virus vector. Crystal and single-particle electron microscopy structures of these antibodies with hemagglutinins from influenza A and B viruses reveal binding to highly conserved epitopes. Collectively, our findings demonstrate that multidomain antibodies targeting multiple epitopes exhibit enhanced virus cross-reactivity and potency. In combination with adeno-associated virus–mediated gene delivery, they may provide an effective strategy to prevent infection with influenza virus and other highly variable pathogens.},
doi = {10.1126/science.aaq0620},
journal = {Science},
issn = {0036-8075},
number = 6414,
volume = 362,
place = {United States},
year = {2018},
month = {11}
}