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Nanobodies with in vitro neutralizing activity protect mice against H5N1 influenza virus infection

Nanobodies with in vitro neutralizing activity protect mice against H5N1 influenza virus infection

Ibanez, Lorena Itati, De Filette, Marina, Hultberg, Anna, Verrips, Theo, Temperton, Nigel, Weiss, Robin A., Vandevelde, Wesley, Schepens, Bert, Vanlandschoot, Peter and Saelens, Xavier (2011) Nanobodies with in vitro neutralizing activity protect mice against H5N1 influenza virus infection. The Journal of Infectious Diseases, 203 (8). pp. 1063-1072. ISSN 0022-1899 (Print), 1537-6613 (Online) (doi:10.1093/infdis/jiq168)

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Abstract

Influenza A virus infections impose a recurrent and global disease burden. Current antivirals against influenza are not always effective. Weassessed the protective potential ofmonovalent and bivalent Nanobodies (Ablynx) against challenge with this virus. These Nanobodies were derived from llamas and target H5N1 hemagglutinin. Intranasal administration of Nanobodies effectively controlled homologous influenza A virus replication. Administration of Nanobodies before challenge strongly reduced H5N1 virus replication in the lungs and protected mice from morbidity and mortality after a lethal challenge with H5N1 virus. The bivalent Nanobody was at least 60-fold more effective than the monovalent Nanobody in controlling virus replication. In addition, Nanobody therapy after challenge strongly reduced viral replication and significantly delayed time to death. Epitope mapping revealed that the VHH Nanobody binds to antigenic site B in H5 hemagglutinin. Because Nanobodies are small, stable, and simple to produce, they are a promising, novel therapeutic agent against influenza.

Item Type: Article
Additional Information: [1] Copyright: © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. [2] Paper presented in part: 14th International Conference on Negative Strand Viruses, Bruges, Belgium, June 2010. Abstract number 307.
Uncontrolled Keywords: influenza virus, nanobodies, H5N1
Subjects: R Medicine > RC Internal medicine
R Medicine > RZ Other systems of medicine
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Medway School of Pharmacy
Related URLs:
Last Modified: 23 Nov 2016 12:22
URI: http://gala.gre.ac.uk/id/eprint/8544

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