Duke-NUS Researchers Discover Potent Dengue-Neutralizing Antibody

A study led by Duke-NUS Medical School has identified a new antibody with exceptional potency against the dengue virus, capable of neutralizing it in very small amounts. The antibody, named 5J7, was shown in the study to be so effective that only 10-9 grams were needed to inhibit the infectivity of dengue virus serotype 3 (DENV-3).

This finding offers potential for the development of effective dengue treatments. Dengue incidence has risen significantly worldwide over the last 50 years, posing a substantial burden on healthcare systems. However, the lack of licensed vaccines or therapeutics is partly due to the existence of four circulating virus serotypes (DENV1-4), which complicate development.

The research, published in Nature Communications, involved isolating 5J7 from approximately 200 candidate antibody molecules by examining blood samples from a dengue-infected patient. High-resolution imaging of the virus-antibody complex revealed that each arm of the antibody can simultaneously bind to three surface proteins on the virus. These binding sites are critical for the virus's ability to invade host cells.

According to Associate Professor Shee Mei Lok, senior author of the study, this unprecedented binding mechanism explains the antibody's high potency. By locking the virus's surface proteins in place, antibody 5J7 prevents the movement necessary for cell invasion, effectively immobilizing the virus.

While antibody 5J7 is effective against DENV-3, further research will consider its efficacy against the remaining dengue serotypes (DENV-2 and DENV-4). The study also touches upon the complexities of secondary dengue infections, where infection with one serotype can potentially enhance disease severity if infected by another serotype later, despite offering lifelong immunity to the first serotype.