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S’pore team discovers 2 antibodies that could neutralise virus strains
 SCIENTISTS in Singapore have moved a step closer to developing a treatment for chikungunya, a disease spread by the Aedes mosquito. They have discovered two monoclonal antibodies – meaning they were developed from single cells – which could neutralise several chikungunya strains in a laboratory setting.
The disease has affected more than 1,000 people here over the past two years. It causes symptoms similar to those seen in dengue, such as fever, joint pains, chills and nausea. These last up to 10 days, although the joint pains may last weeks or even months. Chikungunya then usually goes away on its own. At present, there is no specific treatment for it. Sufferers merely have their symptoms treated, for example with painkillers.
Professor Lucile Warter, who led an international team of 12 scientists from the Singapore Immunology Network (SIgN), and French biopharmaceutical company Vivalis, said the discovery of the antibodies is a big step forward in combating the disease. The research started in August 2009 using B-cells – specialised white blood cells that play a central role in immunity. These cells were taken from a donor infected with chikungunya weeks before, then activated, given the ability to proliferate indefinitely, amplified and cloned.
Scientists then used the cells to identify and generate the antibodies, with the help of Vivalis’ “Humalex”technique. Prof Warter told The Straits Times that this technology was the only one able to identify and generate human monoclonal antibodies. She said such antibodies developed from single cells are more efficient than conventional “polyclonal” drugs developed from multiple cells, and have fewer side effects.
They work by binding to antigens, foreign particles that enter the body. These could be a disease causing agents such as part of a bacterium or virus. Polyclonal antibodies bind to several antigens, making them less effective. By contrast, said Prof Warter, monoclonal antibodies “bind only to specific antigens like two pieces of a puzzle and the two set off a cascade of events leading to the death of the disease”.
In less than a year, the team managed to isolate the target antibodies from the cultured immune cells. The ground-breaking discovery was published in the Journal of Immunology last month. “We were most excited when about 200 of the 2,000 B-cells extracted were binding well with several chikungunya strains in the lab and a few of them had the capability to neutralise the virus,” Prof Warter said.
She added that further testing in vivo – inside a living animal – would have to be carried out to validate the antibodies’ performance as a potential treatment for chikungunya. Prof Warter cautioned that the treatment would not be a vaccine but a passive immunotherapy, which does not stimulate a patient’s immune system to “actively respond to a disease” in the way a vaccine does.
Instead, it is more like a prophylaxis, which is a measure used to prevent the disease rather than cure an existing condition. “Passive immunotherapies are made up of antibodies made outside of the body and re-introduced to the patient to provide immunity against a disease, or to help them fight off an infection,” she said.
SIgN chairman Philippe Kourilsky said: “The combination of the Humalex technology, SIgN’s expertise in human immunology, virology and molecular biology, and Singapore’s location as a hub for Asia helped to speed up the selection, sequencing and characterisation of the most potent antibody candidates.”
Chikungunya is prevalent in Africa, South Asia, and South-east Asia and is transmitted by the Aedes mosquito, the same one that spreads dengue fever. In Singapore, more than 1,000 chikungunya cases were reported between 2008 and last year, according to the Health Ministry statistics on infectious diseases here. There have been no known cases so far this year.
Prof Warter was reluctant to give an exact timeline for when a treatment could be in the market. “It would be safe to say perhaps in the next 10 years,” she finally offered, after much persuasion.
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