Study could lead to vaccines and treatment for dengue virus

July 2, 2015, Vanderbilt University Medical Center
Artistic rendering of the antibody 2D22 neutralizing the dengue virus serotype 2 (DENV-2). Credit: Guntur Fibriansah / Duke-NUS Graduate Medical School Singapore

Researchers at Vanderbilt University and the National University of Singapore have determined the structure of a human monoclonal antibody which, in an animal model, strongly neutralizes a type of the potentially lethal dengue virus.

The finding, reported today July 2 in the journal Science, could lead to the first effective therapies and vaccines against , a complex of four distinct but related mosquito-borne viruses that infect about 390 million people a year and which are a leading cause of illness and death in the tropics.

"Scientists in the antibody discovery group of the Vanderbilt Vaccine Center continue to make great strides in developing novel antiviral drugs, such as this human antibody that not only kills but also prevents enhanced dengue disease," said co-corresponding author and center director James Crowe Jr., M.D., Ann Scott Carell Professor.

The four "serotypes" of dengue are distinguished by different antigens, or proteins on the viral envelope that elicit immune responses. What makes dengue so challenging, and so dangerous, is that generated against one serotype do not protect against the others.

In fact, they actually can enhance infection by a second serotype, a process known as antibody-dependent enhancement (ADE) of infection. Sequential infections increase the risk for and , characterized by fever, vomiting, internal bleeding and potentially fatal circulatory collapse.

The researchers previously generated in the lab against a complex epitope, or antigenic portion of the viral envelope. In the current study, they used cryo-electron microscopy to freeze samples at very low temperatures so they could visualize antibody-antigen binding almost down to the atomic level.

In this way they were able to identify a human monoclonal antibody against dengue virus type 2 (DENV2) that "locked" across an array of envelope proteins. In a mouse model, this prevented the virus from fusing to its target cell, thus it prevents infection.

The antibody also was remarkable in that it has a second major function - it blocks the binding of the other class of antibodies that otherwise would enhance infection.

This specific "epitope," or portion of the envelope proteins elicits a specific immune response, thus it is a potential target for the development of dengue vaccines and therapeutics, the researchers concluded.

Explore further: Team finds powerful dengue neutralizing antibody

More information: Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers, www.sciencemag.org/lookup/doi/ … 1126/science.aaa8651

Related Stories

Team finds powerful dengue neutralizing antibody

February 20, 2015
A new Duke-NUS-led study has identified a super-potent antibody which requires a minute amount to neutralize the dengue virus.

Antibodies discovery could lead to universal dengue vaccine 

December 16, 2014
A major new class of antibodies that can make the four different types of dengue virus (DENV) non-infectious has been discovered by a group of international researchers, including from the University of Melbourne.

Scientists identify the skin immune cells targeted by the dengue virus

June 24, 2015
Cells in the skin immune system that act as 'gateways' enabling the dengue virus to spread through the body have been identified by A*STAR researchers.

Human antibody for dengue virus isolated

June 22, 2012
(Phys.org) -- A group of scientists in Singapore and the UK have isolated a human antibody capable of effectively neutralizing the mosquito-borne dengue virus. Dengue fever is currently incurable and infects an estimated ...

Targeting key cells for a dengue virus infection model

November 5, 2014
Dengue virus infects hundreds of millions of people living in tropical countries every year. Transmitted via mosquito bites, the virus typically causes fever, but may also lead to potentially fatal organ failure. The development ...

Research advances therapy to protect against dengue virus

April 8, 2013
Nearly half of the world's population is at risk of infection by the dengue virus, yet there is no specific treatment for the disease. Now a therapy to protect people from the virus could finally be a step closer, thanks ...

Recommended for you

Tibetan sheep highly susceptible to human plague, originates from marmots

August 16, 2018
In the Qinghai-Tibet plateau, one of the region's highest risk areas for human plague, Himalayan marmots are the primary carriers of the infectious bacterium Y. pestis. Y. pestis infection can be transmitted to humans and ...

Autoimmunity plays role in development of COPD, study finds

August 16, 2018
Autoimmunity plays a role in the development of chronic obstructive pulmonary disease (COPD), according to a study led by Georgia State University and Vanderbilt University Medical Center that analyzed human genome information ...

Scientists identify nearly 200 potential tuberculosis drug targets

August 16, 2018
Tuberculosis is one of the top 10 causes of death worldwide. Nearly 2 million people die every year from this infectious disease, and an estimated 2 billion people are chronically infected. The only vaccine, developed almost ...

Reliable point-of-care blood test can help prevent toxoplasmosis

August 16, 2018
A recent study, performed in Chicago and Rabat, Morocco, found that a novel finger-prick test for infection with the parasite Toxoplasma gondii during pregnancy—and many other potential applications—is 100 percent sensitive ...

First mouse model to mimic lung disease could speed discovery of more effective treatments

August 16, 2018
The biggest hurdle to finding effective therapies for idiopathic pulmonary fibrosis (IPF) – a life-threatening condition in which the lungs become scarred and breathing is increasingly difficult – has been the inability ...

Anticancer drug offers potential alternative to transplant for patients with liver failure

August 15, 2018
Patients suffering sudden liver failure could in the future benefit from a new treatment that could reduce the need for transplants, research published today shows.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.