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Researchers identify the elusive antibody that zaps resilient dengue serotype 2.

A research team from Duke-NUS, Vanderbilt University, the University of North Carolina and the University of California, Berkeley 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.  The new study showed how an antibody neutralises dengue virus serotype 2 (DENV-2).  The team state that this discovery could help with the development of dengue therapeutics.  The study is published in the journal Science.

Previous studies show that the 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.

The current study demonstrated in detail how a potent human derived antibody (2D22) can kill DENV-2. In past research the team 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 from other teams could only kill DENV-2 of a certain morphology, the newly discovered antibody can kill DENV-2 of all morphologies.

The lab previously also identified antibodies that kill DENV1 and DENV3.

The researchers state that 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. They go on to conclude that this clearly illustrates the potential of using this antibody for dengue treatment.

The team’s overall strategy is to develop a safe therapeutic by combining four antibodies that inhibit infection of each of the dengue virus serotypes. The lab 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.

Source:  Duke-NUS Graduate Medical School Singapore (Duke-NUS)

 

Neutralizing Dengue.  This is an artistic rendering of the antibody 2D22 neutralizing the dengue virus serotype 2 (DENV-2).  Credit:  Guntur Fibriansah / Duke-NUS Graduate Medical School Singapore.
Neutralizing Dengue. This is an artistic rendering of the antibody 2D22 neutralizing the dengue virus serotype 2 (DENV-2). Credit: Guntur Fibriansah / Duke-NUS Graduate Medical School Singapore.

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