Researchers develop novel approach to dengue therapy
The research team from MIT's Koch Institute of Integrative Cancer Research set out to develop an antibody for dengue that would target the A strand of the dengue virus' envelope protein. Previous antibodies developed to target the A strand had a high potency but were unable to neutralize all four serotypes of the virus.
Ram Sasisekharan, a biological engineering professor at MIT, and his team analyzed existing antigen complexes to determine how to mutate an antibody that would target the A strand in all four serotypes. After testing the mutated antibody on samples of the four dengue serotypes, the researchers found a 450-fold increase in binding to dengue 4, a 20-fold increase in binding to dengue 2 and lesser improvements in binding to dengue 3 and dengue 1.
"By learning and validating data from numerous three-dimensional structures of interacting antibody and protein complexes, the researchers gained valuable insights that enabled them to redesign a dengue virus envelope antibody to improve its binding by an astounding 450-fold," Subhash Vasudevan, an associate professor at the Singapore-based Duke-NUS Graduate Medical School, said. "The cross-reactive and pan-dengue neutralizing antibody was protective against all four serotypes in cell culture and in an animal model of infection."
The team published the results of the study on Monday in Proceedings of the National Academy of Sciences.
The researchers are preparing for potential preclinical trials and hope to test the mutated antibody on humans within the next two or three years. In the meantime, the researchers will use their immunotherapy approach to test other targets, such as the influenza virus.