Universal dengue vaccine steps closer with antibodies discovery

For the first time, researchers report how they discovered a new class of antibody that could lead to the development of a universal vaccine against dengue - a rapidly emerging, mosquito-borne virus that infects around 400 million people worldwide every year.

Researchers found a new class of antibodies that can neutralize all four types of dengue virus produced from human or mosquito cells.

In the journal Nature Communications, the international team - including members from the University of Melbourne in Australia - reports the first finding of a class of antibody that can neutralize all four types of dengue virus when it is produced from human or mosquito cells.

As well as leading to an effective universal vaccine, the hope is that the discovery will also result in improved laboratory tests that together will reduce the global burden of dengue.

Dengue is a fast-spreading tropical viral infection that is transmitted via mosquitoes. 

Dengue fever can be life-threatening, and there are currently no licensed vaccines or treatments.

Dengue usually causes flu-like symptoms, but sometimes a more severe form can occur. Severe dengue fever is a big killer that affects mainly children in parts of Asia and Latin America. Most of the half million people hospitalized with dengue fever every year are children.

The geographical spread of the disease is increasing. It threatens the Southern US and Australia, and there is also concern of possible spread to Southern Europe.

Dengue virus poses a challenge to antibody recognition

Although infection with one type of dengue leads to life-long protection against that specific form, it offers no protection against the other three types.

The dengue virus poses a particular challenge because its shell changes dramatically over its lifecycle - completed partly in human cells and partly in mosquito cells - making antibody recognition very complicated.

The research team at Melbourne, comments:

"There is an urgent need to reduce incidence of people suffering dengue, and understand the human immune response to infection and the response following vaccination."

The researchers say the study's unique findings make the goal of a dengue vaccine more realistic and may also pave the way for a universal vaccine.

Antibodies 'broadly reactive' against all dengue types in human and mosquito cells

For the study,the researchers studied 145 anti-dengue antibodies from patients infected with dengue virus. They found a new class of antibody that can recognize and bind to a unique structure - known as an epitope - that is present in all four types of dengue virus.

The authors describe the previously unknown epitope as an envelope dimer epitope (EDE) that "bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion."

The antibodies to the epitope were "broadly reactive" across the dengue serotypes and "fully neutralized virus produced in either insect cells or primary human cells," they note.

The findings should clear the way for vaccine trials "in which the induction of antibody to the EDE should be prioritized," they conclude.

In July 2014, another team of researchers reported promising results of the first dengue vaccine widely tested in humans. Reported in The Lancet, the phase 3 clinical trial showed that while efficacy varies across the four types of dengue virus, overall the vaccine protects 56% of subjects from the disease.

References:

1.  A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus, Wanwisa Dejnirattisai et al., Nature Immunology, doi:10.1038/ni.3058, published online 15 December 2014, abstract.
2.  University of Melbourne press release accessed 17 December 2014.