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

Lorena Ibanez (UGent) , Marina De Filette (UGent) , Anna Hultberg, Theo Verrips, Nigel Temperton, Robin A Weiss, Wesley Vandevelde, Bert Schepens (UGent) , Peter Vanlandschoot and Xavier Saelens (UGent)
(2011) JOURNAL OF INFECTIOUS DISEASES. 203(8). p.1063-1072
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Abstract
Influenza A virus infections impose a recurrent and global disease burden. Current antivirals against influenza are not always effective. We assessed the protective potential of monovalent 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.
Keywords
THERAPY, OSELTAMIVIR, GLYCOPROTEINS, THERAPEUTICS, RECOGNITION, BINDING, HEMAGGLUTININ, HONG-KONG, CHAIN ANTIBODIES, A VIRUSES

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Chicago
Ibanez, Lorena, Marina De Filette, Anna Hultberg, Theo Verrips, Nigel Temperton, Robin A Weiss, Wesley Vandevelde, Bert Schepens, Peter Vanlandschoot, and Xavier Saelens. 2011. “Nanobodies with in Vitro Neutralizing Activity Protect Mice Against H5N1 Influenza Virus Infection.” Journal of Infectious Diseases 203 (8): 1063–1072.
APA
Ibanez, L., De Filette, M., Hultberg, A., Verrips, T., Temperton, N., Weiss, R. A., Vandevelde, W., et al. (2011). Nanobodies with in vitro neutralizing activity protect mice against H5N1 influenza virus infection. JOURNAL OF INFECTIOUS DISEASES, 203(8), 1063–1072.
Vancouver
1.
Ibanez L, De Filette M, Hultberg A, Verrips T, Temperton N, Weiss RA, et al. Nanobodies with in vitro neutralizing activity protect mice against H5N1 influenza virus infection. JOURNAL OF INFECTIOUS DISEASES. 2011;203(8):1063–72.
MLA
Ibanez, Lorena, Marina De Filette, Anna Hultberg, et al. “Nanobodies with in Vitro Neutralizing Activity Protect Mice Against H5N1 Influenza Virus Infection.” JOURNAL OF INFECTIOUS DISEASES 203.8 (2011): 1063–1072. Print.
@article{1212323,
  abstract     = {Influenza A virus infections impose a recurrent and global disease burden. Current antivirals against influenza are not always effective. We assessed the protective potential of monovalent 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.},
  author       = {Ibanez, Lorena and De Filette, Marina and Hultberg, Anna and Verrips, Theo and Temperton, Nigel and Weiss, Robin A and Vandevelde, Wesley and Schepens, Bert and Vanlandschoot, Peter and Saelens, Xavier},
  issn         = {0022-1899},
  journal      = {JOURNAL OF INFECTIOUS DISEASES},
  keyword      = {THERAPY,OSELTAMIVIR,GLYCOPROTEINS,THERAPEUTICS,RECOGNITION,BINDING,HEMAGGLUTININ,HONG-KONG,CHAIN ANTIBODIES,A VIRUSES},
  language     = {eng},
  number       = {8},
  pages        = {1063--1072},
  title        = {Nanobodies with in vitro neutralizing activity protect mice against H5N1 influenza virus infection},
  url          = {http://dx.doi.org/10.1093/infdis/jiq168},
  volume       = {203},
  year         = {2011},
}
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