Nanobodies with In Vitro Neutralizing Activity Protect Mice against H5N1 Influenza Virus Infection

LORENA ITATÍ IBAÑEZ; MARINA DE FILETTE; ANNA HULTBERG; THEO VERRIPS; NIGEL TEMPERTON; ROBIN A. WEISS; WESLY VANDEVELDE; BERT SCHEPENS; PETER VANLANDSCHOOT; XAVIER SAELENS

JOURNAL OF INFECTIOUS DISEASES

UNIV CHICAGO PRESS

Lugar: Chicago; Año: 2011 vol. 203 p. 1063 - 1072

0022-1899

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