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

Ibañez, Lorena Itati and De Filette, Marina and Hultberg, Anna and Verrips, Theo and Temperton, Nigel J. and Weiss, Robin A. and Vandevelde, Wesley and Schepens, Bert and Vanlandschoot, Peter and Saelens, Xavier (2011) Nanobodies with in vitro neutralizing activity protect mice against H5N1 influenza virus infection. Journal of Infectious Diseases, 203 (8). pp. 1063-1072. ISSN 00221899 (ISSN) . (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1093/infdis/jiq168

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. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Item Type: Article
Uncontrolled keywords: antivirus agent, Influenza virus hemagglutinin, recombinant influenza H5N1 hemagglutinin nanobody, unclassified drug, animal experiment, animal tissue, article, binding site, controlled study, drug efficacy, epitope mapping, female, in vitro study, influenza A (H5N1), Influenza virus A H5N1, lung, mouse, nonhuman, priority journal, virus neutralization, virus replication, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibody Specificity, Female, Influenza A Virus, H5N1 Subtype, Mice, Mice, Inbred BALB C, Models, Molecular, Nanocapsules, Orthomyxoviridae Infections, Protein Conformation, Specific Pathogen-Free Organisms, Time Factors
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Faculties > Science Technology and Medical Studies > Medway School of Pharmacy
Depositing User: Nigel Temperton
Date Deposited: 02 Aug 2012 10:42
Last Modified: 02 May 2014 11:23
Resource URI: http://kar.kent.ac.uk/id/eprint/29987 (The current URI for this page, for reference purposes)
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