title: Nanobodies with in vitro neutralizing activity protect mice against H5N1 influenza virus infection.
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.
authors: Department for Molecular Biomedical Research, VIB, Ghent University, Technologiepark 927, Ghent, Belgium.
authors: Lorena Itatí
authors: LI
authors: Ibañez
authors: Marina
authors: M
authors: De Filette
authors: Anna
authors: A
authors: Hultberg
authors: Theo
authors: T
authors: Verrips
authors: Nigel
authors: N
authors: Temperton
authors: Robin A
authors: RA
authors: Weiss
authors: Wesley
authors: W
authors: Vandevelde
authors: Bert
authors: B
authors: Schepens
authors: Peter
authors: P
authors: Vanlandschoot
authors: Xavier
authors: X
authors: Saelens
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000918:Antibody Specificity; D005260:Female; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D053769:Nanocapsules; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D011487:Protein Conformation; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D053769:Nanocapsules