Public Release: 

Found: Antibody that zaps resilient dengue serotype

Duke-NUS Medical School

One more piece and we are done! A research team led by the Duke-NUS Graduate Medical School Singapore (Duke-NUS) has found the second-to-last piece of the puzzle needed to potentially cure or treat dengue. This is welcome news as the dengue virus infects about 400 million people worldwide annually, and there is currently no licensed vaccine available to treat it.

Associate Professor Shee-Mei Lok and Research Fellow Guntur Fibriansah, from the Duke-NUS Emerging Infectious Diseases (EID) Programme, led research that showed how an antibody neutralises dengue virus serotype 2 (DENV-2). Published online in Science on 3 July 2015, this discovery could help with the development of dengue therapeutics.

Dengue virus has four serotypes (DENV1-4) circulating in nature, which makes it difficult to treat. To have complete protection against the dengue infection, a vaccine has to simultaneously stimulate an equally strong antibody response against all four serotypes. This, so far, has been proven difficult, as vaccines provide differing levels of protection against the serotypes. Latest clinical trials show good protection against DENV-3 and DEN-4, but poor protection against DENV-1 and no protection, at all, against DENV-2.

In this current work, the EID led team demonstrated, in detail, how a potent human derived antibody (2D22) can kill DENV-2. In past research, Assoc. Prof. Lok has shown that the DENV-2 is more complex than the rest of the dengue serotypes as the mosquito-derived virus has a highly dynamic structure which changes its form, or morphology, as it infects humans. This makes DENV-2 harder to kill. While previously identified antibodies could only kill DENV-2 of a certain morphology, the newly discovered antibody can kill DENV-2 of all morphologies.

"While the injection of other weaker types of antibodies into mice were previously shown to result in the development of more severe symptoms, the new human antibody found in this study not only kills DENV-2, it also prevents the development of severe disease stimulated by the weaker antibodies. This clearly illustrates the potential of using this antibody for dengue treatment," said senior author Assoc. Prof. Lok, whose lab previously also identified antibodies that kill DENV1 and DENV3.

Assoc. Prof. Lok's overall strategy is to develop a safe therapeutic by combining four antibodies that inhibit infection of each of the dengue virus serotypes. Her team is now working on identifying an antibody effective against DENV-4 to complete the full set of antibodies and to use it to make an effective cocktail against all serotypes.

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This research was a collaboration between researchers from Duke-NUS, Vanderbilt University, the University of North Carolina and the University of California, Berkeley.

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