Ibañez, L.I. and De Filette, M. and Hultberg, A. and Verrips, T. and Temperton, N.J. and Weiss, R.A. and Vandevelde, W. and Schepens, B. and Vanlandschoot, P. and Saelens, X. (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) .
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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. Â© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
|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:||06 Aug 2012 09:02|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/29987 (The current URI for this page, for reference purposes)|
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