Recent breakthroughs in Chikungunya research spearheaded by scientists at A*STAR's Singapore Immunology Network (SIgN) have made great strides in the battle against the infectious disease. Working in close collaborations with Singapore clinician-scientists and international researchers , Dr Lisa Ng, Principal Investigator of the Chikungunya research group at SIgN, led the team to discover a direct biomarker which serves as an early and accurate prognosis of patients who have a higher risk of the more severe form of Chikungunya fever (CHIKF). This means that doctors can now quickly and accurately identify patients at risk, facilitating a more targetted treatment and clinical care at the onset of the disease.
Chikungunya fever, caused by the Chikungunya virus (CHIKV) , is a mosquito-borne, infectious disease endemic to Southeast Asia and Africa. Since its re-emergence in 2005, CHIKV infection has spread to nearly 20 countries to infect millions . Singapore, for instance, was hit twice by Chikungunya fever outbreaks in January and August 2008.
CHIKV infection is characterised by an abrupt onset of fever frequently accompanied by severe muscle and joint pains. Though most patients recover fully within a week, in severe cases, the joint pains may persist for months, or even years. For individuals with a weak immune system, the disease can result in death. With no clinically-approved vaccine or treatment for Chikungunya fever, it remains a worrying public health problem.
To devise strategies to stop CHIKV transmission, Dr Ng's team collaborated with Professor Leo Yee Sin and Dr Angela Chow, clinician-scientists from the Communicable Disease Centre (CDC) at Tan Tock Seng Hospital , to study how the human body responds to CHIKV infection. The team conducted a comprehensive study on the antibody response against CHIKV in patients. They discovered that patients who respond to the disease at the onset with high levels of Immunoglobulin G3 (IgG3), a naturally-acquired antibody, are protected from the more severe form of Chikungunya fever, characterised by persistent joint pains. On the other hand, patients with a delayed IgG3 response generally have less acute symptoms at the start, but are more susceptible to chronic debilitating joint pains at later stage of the disease. Hence, the IgG3 antibodies serve as a specific biomarker of patients with increased risk of the severe form of the disease.
Collaborating with computational experts from A*STAR's Institute for Infocomm Research (I2R), Dr Ng's team also uncovered that a very small defined segment of the Chikungunya viral protein, named "E2EP3", was able to induce the natural IgG3 protective response in preclinical models. They found that mice vaccinated with the E2EP3 peptides were protected against CHIKV with significant reduction in viral counts and joint inflammation. This finding raises hope for a new effective Chikungunya vaccine that can offer protection against Chikungunya virus in the event of an outbreak.
Dr Ng said, "Long-term treatment required for the chronic joint pain in Chikungunya-infected patients places social and economic burden for both patients and the public healthcare system. We are excited that the mechanistic insights gained through our collaborative research with the local hospitals and international research partners have led to discovery of 'new weapons' to tackle Chikungunya more effectively."
Scientific Director of SIgN, Professor Paola Castagnoli said, "With increasing threat of Chikungunya virus infection, particularly in Asia and the Pacific region, this significant breakthrough is a step forward in enhancing our pandemic preparedness against the infectious disease. This is a testament to the successful collaborations between research scientists and clinicians in translating scientific discoveries into impactful healthcare solutions for the benefit of Singapore and beyond. "
 Dr Ng has collaborations with Dr Pierre Roques from CEA, France and Dr Jamal I-Ching Sam from the University of Malaya through the Integrated Chikungunya Research (ICRES) consortium network, which is headed by Professor John K. Fazakerley from The Roslin Institute, Centre for Infectious Diseases, the UK. ICRES consortium, supported by the European Union (EU) Framework Program 7 (FP7), is a platform for international collaborations where significant research breakthroughs in CHIKF can be further expanded into new strategies to monitor, detect, treat and protect the world-wide community from the threat of CHIKV.
CHIKV, an alphavirus that is transmitted by infected Aedes mosquitoes, was first isolated in 1953 in Tanzania from infected patients who often developed a contorted posture owing to debilitating joint pains. The name Chikungunya means 'that which bends up' in the Makonde language of Southern Africa.
http://www.cdc.gov/ncidod/dvbid/chikungunya/ and http://www.promedmail.org/
Notes for editor:
1. Dr Lisa Ng's research group at SIgN focusses on the human body's immune responses to vector-borned diseases that are epidemic or highly endemic in the tropical region. Broadening her scope from the immunological stand-point, Dr Ng works closely with clinicians and public health experts in developing infectious disease preparedness through vaccines, diagnostic kits, and therapeutic antibodies. For her significant scientific contributions to research on infectious diseases, Dr Ng is the first Singaporean and woman scientist to be awarded the ASEAN Young Scientist and Technologist Award in 2008. As Adjunct Professor with the Department of Biochemistry, Yong Loo Lin School of Medicine at the National University of Singapore, and at the Duke-NUS Graduate Medical School, Dr Ng also takes personal interest in mentoring undergraduate and postgraduate students.
2. The research findings described in this media release can be found in the 2 March 2012 issues of the following scientific journals:-
I. The Journal of Infectious Diseases under the title, "Early Appearance of Neutralizing Immunoglobulin G3 Antibodies Is Associated With Chikungunya Virus Clearance and Long-term Clinical Protection" by Yiu-Wing Kam1, Diane Simarmata1, Angela Chow2,3, Zhisheng Her1,4, Terk-Shin Teng1, Edward K. S. Ong1, Laurent Rénia1,Yee-Sin Leo2 and Lisa F. P. Ng1,4
1 Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore
2 Communicable Disease Centre, Tan Tock Seng Hospital, Singapore
3 Department of Epidemiology and Public Health
4 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore
Full text of the article can be accessed from http://jid.oxfordjournals.org/content/early/2012/02/08/infdis.jis033.full.pdf+html
II. EMBO Molecular Medicine under the title, "Early Neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein" by Yiu-Wing Kam1*, Fok-Moon Lum1,2*, Teck-Hui Teo1*, Wendy W. L. Lee1, Diane Simarmata1, Sumitro Harjanto1,3, Chong-Long Chua4, Yoke-Fun Chan4, Jin-Kiat Wee1,3, Angela Chow5, Raymond T. P. Lin6, Yee-Sin Leo5, Roger Le Grand7, I-Ching Sam4, Joo-Chuan Tong2,3, Pierre Roques7, Karl-Heinz Wiesmüller8, Laurent Rénia1, Olaf Rötzschke1, Lisa F. P. Ng1,2
1 Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore
2 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
3 Data Mining Department, Institute for Infocomm Research, A*STAR Fusionopolis, Singapore, Singapore
4 Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
5 Communicable Diseases Centre, Tan Tock Seng Hospital, Singapore, Singapore
6 National Public Health Laboratory, Communicable Diseases Division, Ministry of Health, Singapore, Singapore
7 Division of ImmunoVirology (SIV), Institute of Emerging Diseases and Innovative Therapies (IMETI), CEA, Fontenay-aux-Roses, France
8 EMC Microcollections GmbH, Tübingen, Germany
* These authors contributed equally to this work
Abstract of this article can be accessed from http://onlinelibrary.wiley.com/doi/10.1002/emmm.201200213/abstract
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About the Singapore Immunology Network (SIgN)
The Singapore Immunology Network (SIgN), officially inaugurated on 15 January 2008, is a research consortium under the Agency for Science, Technology and Research (A*STAR)'s Biomedical Research Council. The mandate of SIgN is to advance human immunology research and participate in international efforts to combat major health problems. Since its launch, SIgN has grown rapidly and currently includes 200 scientists from 25 different countries around the world working under 20 renowned principal investigators. At SIgN, researchers investigate immunity during infection and various inflammatory conditions including cancer and are supported by cutting edge technological research platforms and core services.
Through this, SIgN aims to build a strong platform in basic human immunology research for better translation of research findings into clinical applications. SIgN also sets out to establish productive links with local and international institutions, and encourage the exchange of ideas and expertise between academic, industrial and clinical partners and thus contribute to a vibrant research environment in Singapore. For more information about SIgN, please visit www.sign.a-star.edu.sg.
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences and physical sciences and engineering research institutes, and six consortia & centres, located in Biopolis and Fusionopolis as well as their immediate vicinity.
A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, and with other local and international partners. For more information about A*STAR, please visit www.a-star.edu.sg.
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