New antibody discovery holds promise for dengue vaccine

5 Jul

Worldwide, there are around 390 million cases of dengue a year – a potentially deadly mosquito-borne virus. But according to a new study published in the journal Science, researchers have made a discovery that could lead to a vaccine and treatments for the condition.
The researchers have discovered an antibody that prevented dengue infection in mouse models, bringing us closer to a vaccine for the virus.

Study co-author Dr. James Crowe Jr., of Vanderbilt University in Nashville, TN, and colleagues have uncovered a human antibody that prevented dengue in mouse models by stopping the virus from binding to target cells.

“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 dengue virus but also prevents enhanced dengue disease,” says Dr. Crowe Jr.

Dengue is transmitted by a bite from a mosquito – most commonly the Aedes aegypti mosquito – that is infected with one of four dengue virus serotypes, known as DENV1-4.

Symptoms of dengue include fever, severe headache, joint pain, muscle and bone pain, severe pain behind the eyes and mild bleeding – such as nose bleed. A more severe form of the virus is known as dengue hemorrhagic fever (DHF), characterized by prolonged fever, abdominal pain, persistent vomiting, bleeding and breathing problems.

According to the World Health Organization (WHO), more than 22,000 people worldwide die from dengue each year, the majority of whom are children.

At present, there are no vaccines or specific medications for dengue. Symptoms are usually treated with painkillers such as acetaminophen, and fluid replacement therapy may be effective if the virus is identified early enough.

2D22 antibody prevented dengue infection in mouse models

Though researchers are working hard to find prevention and treatment strategies for dengue, they face challenges. Dengue’s four serotypes consist of different antigens, which means antibodies that are effective against one serotype may not be effective against others.

Dr. Crowe and colleagues note that such antibodies can also “cross-react,” leading to infection with a second serotype and raising the risk of DHF.

In previous research, the team created human monoclonal antibodies (HMAbs) that could bind to the antigenic section of the “epitope,” or viral envelope, of the DENV2 serotype. The epitope is the part of an antigen that is recognized by immune cells.

For this latest study, the team used cryo-electron microscopy to freeze samples of the HMAbs, allowing them to see how the antibodies bind to the epitopes at an “atomic level.”

The researchers identified an HMAb called 2D22 that was able to bind to a variety of epitope proteins of the DENV2 serotype, and in mouse models, the antibody stopped the virus from fusing to its target cell, preventing infection.

What is more, the researchers found the 2D22 antibody also prevented cross-reaction of other antibodies, which reduced the risk of infection with a second dengue serotype.

Based on their findings, the team concludes that “the epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.”

In December 2014, another study reported by Medical News Today showed promise for a dengue vaccine. Published in Nature Immunology, the study detailed the discovery of an antibody that can neutralize all four dengue serotypes.

The researchers of that study – including investigators from the University of Melbourne in Australia – say their findings may open the door to a universal vaccine for the virus.

Written by Honor Whiteman