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Dealing with dengue

Getting closer to developing a vaccine...

New research at The University of the West Indies (UWI) could provide the key to developing a dengue vaccine—a problem that has stumped scientists for decades.
Development of a dengue vaccine has unique challenges. There are four known distinct serotypes of the dengue virus (dengue 1-4). A person who recovers from an infection by one serotype becomes immune to it. They still, however, remain susceptible to infection by any of the other serotypes of the virus. In fact, if after recovering from infection, they are later infected with another serotype, they would be at least 15 times more likely to develop the more severe, potentially fatal dengue haemorrhagic fever (DHF). A successful vaccine would therefore have to be tetravalent and protect against all four serotypes.
The World Health Organisation (WHO) lists dengue as an orphan disease—a disease which provides a market so small for drug therapy that it attracts limited pharmaceutical investment in research and development. Still, there have been some clinical trials of vaccines, including those of tetravalent vaccines in the Far East. So far, however, scientists have had little success producing a synthetic vaccine that controls dengue infection.
Today, researchers at The University of the West Indies (UWI), St Augustine, believe they may have found a way to combat all four serotypes with one vaccine.
“At the outset of our research efforts, we concluded that a traditional approach to this problem would almost inevitably meet with failure,” said Gurdial Singh, professor in UWI’s Department of Chemistry. “We required out of the box thinking and the belief that we could succeed in this venture where a large number of research teams had failed.”
Central to the approach, which is built on the findings of earlier researchers and commercial organisations, is an understanding of the protein structure of the virus. There is a carbohydrate attached to the protein on the surface of the dengue virus—the envelope protein. This carbohydrate is common to all four serotypes. This commonality among the serotypes is what UWI researchers believe makes these surface carbohydrates key to developing a vaccine.
In all important biological processes, cells communicate with each other through the interaction of surface carbohydrates. These processes allow the virus to reproduce and target host cells. Each surface carbohydrate consists of six sugars. How these sugars are linked together is critical to the survival of the virus and its subsequent interaction with the host cells. Being able to duplicate the six sugars and create these surface carbohydrates would mean that antibodies could be raised to combat all four serotypes of the virus.
The work at UWI involves developing a new universal phosphorylation methodology that is based upon how nature makes carbohydrates.
“We mimicked RNA and DNA in nature,” Prof Singh explained. Researchers have applied this strategy to a series of targets and are currently engaged in the preparation of the Dengue virus E-protein carbohydrates.
“We have been able to synthesise the sugars and gotten two of them to link together,” Prof Singh said. “We could have all six linked in about a year.”
While there are no guarantees in the research process, Prof Singh is confident that an effective vaccine is within reach. “Once we have gram amounts of this material we will join with other teams across the world and raise new antibodies that will be effective against the dengue virus,” he said.
As temperatures rise due to climate change and global warming, the rate of dengue infection is likely to spread to northern climates and become a major concern in the Caribbean.
Because there is currently no vaccine to prevent infection, controlling the spread of the dengue virus has meant controlling the Aedes aegypti mosquito vector. This method has met with limited success.
However, Prof Singh is not daunted and remains optimistic about the potential impact of this research.
“Despite the challenges, we are continuing our research efforts. I am confident that we are getting closer to developing a vaccine and this will be a significant breakthrough for reducing the number of persons likely to get infected with the dengue virus in the future. This is what continues to drive our work.”

For more information on this project, please contact Prof Gurdial Singh at gurdial.singh@sta.uwi.edu

For information on all UWI St Augustine research, please visit www.sta.uwi.edu
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