A DUKE-NUS study led by Associate Professor Shee Mei Lok has identified a super-potent antibody called 5J7 which even in minute amounts can neutralize Dengue serotype 3 virus (DENV-3) and prevent infection. This study was published in the journal Nature Communications and gives hope for the development of effective dengue treatments.
Dengue Fever is an illness caused by infection with a virus transmitted by the Aedes mosquito. There are four serotypes of this virus (DENV-1, DENV-2, DENV-3 and DENV-4) which can infect and cause various symptoms such as fever, join pain, rashes and in severe cases, bleeding and shock. The incidence of Dengue has increased by 30 times world-wide over the past 50 years and still there is no effective vaccine or therapeutic agent available. This is because an effective vaccine should be ideally targeting all the four circulating virus serotypes (DENV 1-4) which hasn’t been successful yet.
A/Prof Lok’s lab has been working on developing effective therapeutics by understanding the pathology and structure of the Dengue virus. Their lab has already discovered antibodies that are effective against DENV-1.
In this study, researchers isolated 5J7 from 200 different candidate antibody molecules by studying blood samples from a dengue infected patient. By examining the virus-antibody complex structure at very high magnification, they showed that each arm of the antibody is surprisingly effective in grabbing three surface proteins on the surface of the virus at the same time. In addition, the sites on the virus where the antibody was bound were critical for the virus to invade cells.
“This kind of binding with the virus has never been observed and it explains why the antibody itself is so highly potent.” said A/Prof Lok.
“The movement of virus surface proteins is highly essential for invading cells – you can think of antibody 5J7 locking the virus surface proteins, thus strapping the virus.”
Although they have potent antibodies against DENV-1 and DENV-3, the remaining two serotypes of dengue virus (DENV-2 and DENV-4) have to be considered. When a patient is infected by one serotype- it stimulates the production of a variety of antibodies that kills that serotype and the patient develops a lifetime immunity towards that serotype. However, in the course of infection, the patient will also produce antibodies that will bind the other three if they are infected by them. This may enhance their secondary infection and cause the development of a more severe form of the disease.
“We need to test the efficacy in mouse models first and then move to clinical trials,” said A/Prof Lok about the next step after this promising finding. “We are optimistic that we will make a treatment breakthrough within these few years but antibodies against all the other serotypes have to be identified first.”
The original publication can be accessed here.