Scientists have discovered a new class of human antibodies
against the dengue fever virus, which could be exploited to develop
a vaccine.
Dengue fever cases have risen dramatically in recent decades as
the disease has spread to new areas. An estimated 390 million
infections occur each year, with around 40 per cent of the world's
population living in areas at risk. In most cases it causes
flu-like illness, but in some patients it develops into dengue
haemorrhagic fever, which can lead to shock, haemorrhage and
death.
Studying blood from people infected with dengue in southeast
Asia, researchers at Imperial College London examined the
antibodies produced by the patients' immune systems. Antibodies are
large proteins that recognise specific parts of foreign objects
such as bacteria and viruses and signals to other parts of the
immune system to attack the invader.
The researchers identified a new class of antibodies that is
effective against all four strains of dengue virus. These
antibodies could themselves be used to protect against or treat
infections; or vaccines could be devised to stimulate the body to
produce these antibodies.
The study (published in Nature Immunology) was led by Professor
Gavin Screaton and Dr Juthathip Mongkolsapaya at Imperial in
collaboration with Dr Felix Rey and his colleagues at the Institut
Pasteur in Paris. In a second paper, published in Nature, the
researchers analysed the antibodies' structure, which is of crucial
importance for vaccine development.
Professor Screaton said: "The incidence of dengue continues to
increase despite attempts to control its spread. Outbreaks of
dengue put huge stresses on the healthcare systems of endemic
countries and a vaccine is desperately needed to check the disease.
Current vaccine trials have shown some promise but do not fully
protect from infection. The finding of this new class of antibodies
points the way for a new approach to a dengue vaccine design which
we are pursuing."
Rather than binding to a single protein on the surface of the
virus, these antibodies target a molecular bridge between two
proteins. Although the four strains of dengue virus have variations
in their surface proteins, the molecular bridge is the same,
enabling the antibodies to neutralise all the different types. A
vaccine containing the bridge, or a closely similar molecule, could
work by training the immune system to recognise and attack dengue
viruses.
A
new class of highly potent, broadly neutralizing antibodies
isolated from viremic patients infected with dengue virus is
published in Nature Immunology.