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A long-standing mystery surrounding the rising scourge of dengue fever — why it is much more dangerous to catch it for a second time — has been resolved by scientists.

Dengue fever is a potentially fatal, mosquito-borne disease whose incidence has been on the rise, threatening two-fifths of the world's population mainly in the tropics and sub-tropics, according to the WHO.

The risk of developing a life-threatening complication — dengue haemorrhagic fever — is higher during a second infection, a problem that has complicated efforts to develop a vaccine. But the reason for this has evaded explanation so far.

Now, scientists working to unravel this mystery have found that certain antibodies produced by the immune system to fight the dengue virus do not protect against a repeated infection. Instead they help the virus to infect the body, causing severe health problems, scientists report.

The finding could help develop an effective and safe vaccine as it provides "some key information about what is and what is not likely to work when trying to combat the dengue virus," said researchers in the United Kingdom and Thailand, who published their results in Science (7 May).

After analysing blood samples donated by infected volunteers, the researchers identified antibodies that their immune systems had made against the dengue virus. The body normally produces antibodies that attack viruses but these precursor membrane protein (prM) antibodies unexpectedly boosted replication of the dengue virus during a second infection.

The antibodies recognise different strains of virus, but are not specific enough to prevent infection, and in fact help the virus enter the host cells where it replicates and causes further infection.

So far there is no vaccine against dengue fever but several candidates are in clinical trials (see Study reviews dengue vaccine candidates).

Since most of the vaccines elicit the response of these prM antibodies, there are now concerns that vaccines might predispose people to develop dengue haemorrhagic fever.

"Most of the leading vaccine candidates contain sequences for both the dengue prM and envelope [the protein cover of many viruses]," Gavin Screaton, chair of medicine at Imperial College London, UK, and co-author of the study, told SciDev.Net.

"The prM antibodies can be harmful, so an ideal vaccine would attempt to minimise these while still stimulating antibodies against the envelope, which is likely to be the most protective," he added.

Sarah Rowland-Jones, an immunologist at the Weatherall Institute of Molecular Medicine, University of Oxford, UK, described the study as "exciting".

"This is a very important finding which helps resolve the controversy about why severe cases are much more likely to occur when people have been infected previously with a different dengue virus strain, and will provide a clear indication of the kind of immune response that should be avoided in dengue virus vaccines," she told SciDev.Net.

References

Science 328, 745-748 (2010)

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