Antibody That Targets DENV-2 Found

Unlike other DENV-2 binding antibodies, 2D22 is able to kill DENV-2 viruses of all morphologies.

AsianScientist (Jul. 10, 2015) – Researchers have found an antibody that can neutralize the complex DENV-2 serotype. Published in Science, their findings 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 each serotype. Latest clinical trials show good protection against DENV-3 and DEN-4, but poor protection against DENV-1 and no protection against DENV-2.

In this current work, Associate Professor Lok Shee-Mei and Research Fellow Guntur Fibriansah, from the Duke-NUS Graduate Medical School Singapore (Duke-NUS) Emerging Infectious Diseases (EID) Program, demonstrated how a potent human derived antibody (2D22) can kill DENV-2.

In past research, Lok and colleagues showed that the DENV-2 is more complex than the rest of the dengue serotypes as the virus has a highly dynamic structure which changes its morphology as it infects humans. While previously identified antibodies could only kill DENV-2 of a certain morphology, the newly identified 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 Lok, whose lab previously also identified antibodies that kill DENV1 and DENV3.

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.

The article can be found at: Fibriansah et al. (2015) Cryo-EM Structure of an Antibody that Neutralizes Dengue Virus Type 2 by Locking E Protein Dimers.

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Source: Duke-NUS.
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