Engineering a potential treatment for all four dengue serotypes

(L-R) Prof Peter Dedon, SMART PI and A/Prof Eng Eong Ooi, Duke-NUS Dy Director of Emerging Infectious Diseases Programme

A multinational research team comprising scientists, engineers and drug developers have joined forces to develop a viable dengue therapeutic that targets all dengue serotypes1. This is welcome news as dengue now spans the entire tropical world and an estimated 400 million people are infected each year. Despite the numbers, there remains no licensed treatment for dengue patients. However, this problem may soon be solved by promising findings published in the prestigious journal, Cell.

Researchers from the Singapore-MIT Alliance for Research and Technology (SMART), Duke-NUS Graduate School of Medicine (Duke-NUS), National University of Singapore (NUS) and Nanyang Technological University (NTU) have collaborated with the Massachusetts Institute of Technology (MIT) and a biotechnology company, Visterra, to develop a single treatment.

The team started with a naturally occurring antibody that reacted only against limited number of types of dengue virus. Using that antibody as a scaffold, the team engineered a new antibody that reacts against all four types of dengue virus. The engineering was made possible by computational methods developed in MIT and SMART. This was then confirmed and validated using a detailed crystal structure of the antibody-virus protein complex obtained at NTU, which also provided insights into how the antibody engaged the virus to produce the desired effect.

Using a variety of systems developed in the SMART laboratories in the Campus for Research Excellence And Technological Enterprise (CREATE) (e.g. the SMART humanised mouse model), Duke-NUS and NUS, the team then showed that this novel antibody has the potential to neutralise dengue virus and prevent signs of disease.

Another important feature of this antibody is that it acts on a part of the virus that is not normally targeted by the normal human immune response. This is important as the antibody would not need to compete with but would instead augment the overall natural immune response against dengue virus. See News Release for more.

This story was featured in the media: TODAY and AsiaOne.