New understanding of dengue fever could help with vaccine

Study shows that some of the human immune system's defences against the virus that causes dengue fever actually help the virus to infect more cells <em> - News Release</em>

Imperial College London News Release

Under STRICT EMBARGO for
14.00 U.S. Eastern Time / 19.00 UK Time
Thursday 6 May 2010

Some of the human immune system's defences against the virus that causes dengue fever actually help the virus to infect more cells, according to new research published today in the journal Science.

The researchers behind the work, from Imperial College London, hope their new findings could help with the design of a vaccine against the dengue virus. The study also brings scientists closer to understanding why people who contract dengue fever more than once usually experience more severe and dangerous symptoms the second time around.

Dengue fever is transmitted by a mosquito bite and is prevalent in sub-tropical and tropical regions including South East Asia and South America. Symptoms include high fever, severe aching in the joints and vomiting. The dengue virus can also cause hemorrhagic fever, which can be fatal.

Incidence of dengue fever has increased dramatically in the last century and two fifths of the world's population are now at risk from it, according to the World Health Organisation. There are four distinct strains of the virus and no licensed vaccines or drugs have yet been developed to combat any of them.

The researchers behind today's study have identified a set of antibodies, produced by the human immune system to fight off the dengue virus, that they believe scientists should avoid including in any new vaccine to prevent dengue fever.

Dengue fever is transmitted by a mosquito bite

The new research shows that these precursor membrane protein (prM) antibodies do not do a very effective job of neutralising the virus. Moreover, these antibodies actually help the virus to infect more cells.

The study suggests that when a person who has already been infected with one strain of dengue virus encounters a different strain of dengue virus, the prM antibodies awakened during the first infection spring into action again. However, rather than protecting the body from the second infection, these prM antibodies help the virus to establish itself.

This activity of the prM antibodies could explain why a second infection with a different strain of the virus can cause more harm than the first infection. The researchers believe that if a dengue virus vaccine contained prM antibodies, this could cause similar problems.

Professor Gavin Screaton, the lead author of the study who is the Head of the Department of Medicine at Imperial College London, said: "A huge proportion of the world's population is at risk from dengue fever and although treatments have improved, it can be a very unpleasant, painful disease and people are still dying from it. When there is an epidemic of dengue fever, it can put a huge strain on health systems and local economies as well as on individuals and their families.

"Our new research gives us some key information about what is and what is not likely to work when trying to combat the dengue virus. We hope that our findings will bring scientists one step closer to creating an effective vaccine," he added.

The researchers reached their conclusions after analysing individual antibodies to the dengue virus extracted from blood samples donated by infected volunteers.

This study was a collaboration between researchers at Imperial College London, UK and Mahidol University, Khon Kaen Hospital and Songkhla Hospital in Thailand.

The work was supported by the Medical Research Council, UK; the Wellcome Trust, UK; the National Institute for Health Research Biomedical Research Centre funding scheme; the Thailand Tropical Disease Research Program T2; and the Thailand National Centre for Genetic Engineering and Biotechnology.

-ends-

For further information please contact:

Laura Gallagher
Research Media Relations Manager
Imperial College London
e-mail: l.gallagher@imperial.ac.uk
Telephone: +44 (0)207 594 8432 or ext. 48432
Out of hours duty Press Officer: +44 (0)7803 886 248

1. "Cross-reacting Antibodies Enhance Dengue Virus Infection in Humans," Science, Thursday 6 May 2010

Corresponding author: Professor Gavin Screaton, Imperial College London (for full list of authors please see paper).

2. The Wellcome Trust is a global charity dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk

3. For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk

4. Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve health in the UK and globally, tackle climate change and develop clean and sustainable sources of energy.