A new Duke-National University of Singapore (Duke-NUS)-led study has identified a super-potent human monoclonal antibody that requires just a minute amount to neutralize the dengue virus. This significant advance, published online on February 20, 2015, in an open-access article in Nature Communications, shows how a newly identified antibody, 5J7, is highly effective in killing dengue virus; only 10-9 g of antibody is needed to stop the infection of dengue serotype 3 virus (DENV-3). The authors report that DENV-specific antibody 5J7 is exceptionally potent, neutralizing 50% of virus at nanogram-range antibody concentration. This new finding gives hope for the development of effective dengue treatments. The authors further report that cryo-electron microscopy analysis of the Fab 5J7–DENV complex shows that a single Fab molecule binds across three envelope proteins and engages three functionally important domains, each from a different envelope protein. These domains are critical for receptor binding and fusion to the endosomal membrane. The ability to bind to multiple domains allows the 5J7 antibody to fully coat the dengue virus surface with only 60 copies of Fab, that is, half the amount compared with other potent antibodies. The authors say that their study of 5J7 reveals a highly efficient and unusual mechanism of molecular recognition by an antibody. Their article is titled “A Highly Potent Human Antibody Neutralizes Dengue Virus Serotype 3 by Binding across Three Surface Proteins.” Over the last 50 years, the incidence of dengue virus infection has increased by 30 times worldwide. The virus causes fever, rashes, and joint pain and, in severe cases, bleeding and shock. It is estimated to be endemic in 100 countries and is a huge burden on healthcare systems.
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