Nanobodies With In Vitro Neutralizing Activity Protect Mice Against H5N1 Influenza Virus Infection.
Summary of "Nanobodies With In Vitro Neutralizing Activity Protect Mice Against H5N1 Influenza Virus Infection."
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.
Affiliation
Department for Molecular Biomedical Research, VIB.
Journal Details
This article was published in the following journal.
Name: The Journal of infectious diseases
ISSN: 1537-6613
Pages: 1063-72
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21450996
- DOI: http://dx.doi.org/10.1093/infdis/jiq168
Medical and Biotech [MESH] Definitions
Antibodies, Neutralizing
Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.
Inhibitory Concentration 50
The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.
Mice, 129 Strain
Strains of mice arising from a parental inbred stock that was subsequently used to produce substrains of knockout and other mutant mice with targeted mutations.
Mice, Scid
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Mice, Inbred Cftr
A strain of mice widely studied as a model for cystic fibrosis. These mice are generated from embryonic stem cells in which the CFTR (cystic fibrosis transmembrane conductance regulator) gene is inactivated by gene targeting. As a result, all mice have one copy of this altered gene in all their tissues. Mice homozygous for the disrupted gene exhibit many features common to young cystic fibrosis patients, including failure to thrive, meconium ileus, and alteration of mucous and serous glands.
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