Engineered Antibody Neutralizes All Four Dengue Serotypes

Researchers have designed an antibody that targets all four serotypes of dengue, sparking hopes for the first viable dengue therapeutic

A multinational research team comprising scientists, engineers and drug developers have joined forces to develop a viable dengue therapeutic that targets all dengue serotypes. Their results, published in Cell, come as welcome news at a time were an estimated 400 million people are infected with dengue each year.

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 for all four serotypes of dengue.

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.

“This interdisciplinary, transnational team has enabled us to address this problem in unique ways,” said Professor Ram Sasisekharan, SMART principal investigator (PI) of the Infectious Diseases Interdisciplinary Research Group (ID IRG), and MIT Professor of Biological Engineering and Health Sciences & Technology, who led the team. “A single laboratory would not have the breadth of expertise to solve this problem on its own.”

“We have each been working on our own areas of interests for years,” added Associate Professor Ooi Eng Eong, deputy director of the Emerging Infectious Diseases Programme at Duke-NUS and SMART co-lead PI of ID IRG. “To be able to take what we have built over the years and put it together to solve a critical medical need, has been very rewarding personally and professionally.”

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