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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
On a mouse monoclonal antibody that neutralizes all four dengue virus serotypes
Journal of General Virology, Volume 90, No. 4, Year 2009
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Description
The flavivirus envelope glycoprotein (E) is responsible for viral attachment and entry by membrane fusion. Its ectodomain is the primary target of the humoral immune response. In particular, the C-terminal Ig-like domain III of E, which is exposed at the surface of the viral particle, forms an attractive antigen for raising protective monoclonal antibodies (mAb). 9F12, a mouse mAb raised against a dengue virus (DENV) serotype 2 recombinant domain III, cross-reacts with corresponding domains from the other three DENV serotypes and also with West Nile virus. mAb 9F12 binds with nanomolar affinity to a conserved epitope that maps to the viral surface comprising residues 305, 307, 310 and 330 of the E protein. mAb 9F12 neutralizes all four DENV serotypes in plaque reduction assays. We expressed a single-chain Fv from 9F12 that retains the binding activity of the parent mAb. Adsorption and fusion inhibition assays indicate that mAb 9F12 prevents early steps of viral entry. Its virus inhibition activity and broad cross-reactivity makes mAb 9F12 a suitable candidate for optimization and humanization into a therapeutic antibody to treat severe infections by dengue. © 2009 SGM.
Authors & Co-Authors
Nkenfou, Céline Nguefeu
Singapore, Singapore City
Novartis Institute for Tropical Diseases Pte. Ltd.
Schul, Wouter
Singapore, Singapore City
Novartis Institute for Tropical Diseases Pte. Ltd.
Diamond, Michael S.
United States, St. Louis
Washington University School of Medicine in St. Louis
Vasudevan, Subhash G.
Australia, Townsville
James Cook University
Singapore, Singapore City
National University of Singapore
Lescar, Julien
Singapore, Singapore City
Nanyang Technological University
France, Marseille
Laboratoire Architecture et Fonction Des Macromolécules Biologiques
Statistics
Citations: 74
Authors: 5
Affiliations: 6
Identifiers
Doi:
10.1099/vir.0.006874-0
ISSN:
14652099
Research Areas
Infectious Diseases