Microsoft word - press_release_malaria_research breakthrough_.doc

30 JULY 2009


New findings could lead to the development of urgently needed vaccine for
widespread mosquito-borne disease

Scientists have developed a novel immunisation method that will induce fast and effective protection in humans against the life-threatening malaria parasite, Plasmodium falciparum1. The findings of Associate Professor Laurent Renia from A*STAR’s Singapore Immunology Network (SIgN) and his counterparts in the Netherlands and France were published in the prestigious New England Journal of Medicine on 30 July 2009 under the title, “Protection against a malaria challenge by sporozoite inoculation”. This discovery could contribute significantly to the development of an effective vaccine for the infectious disease that infects 350m to 500m people world-wide and kills over 1m people each year. The scientists’ experimental approach involved exposing two groups of healthy human subjects to mosquitoes once a month over a three-month period2. One group was exposed to mosquitoes infected with the malaria parasite, P. falciparum (vaccine group), and the other group to uninfected mosquitoes (control group). During the period of exposure, the human subjects were administered with chloroquine, an anti-malaria drug that prevented P. falciparum from multiplying in the blood. Eight weeks after the last round of immunisation and four weeks3 after the discontinuation of chloroquine administration, the subjects from both groups were re- 1 Of the five malaria parasite species that can cause malaria in humans, Plasmodium falciparum (P. falciparum) is the most common cause of infection and is responsible for about 80% of all human malaria cases and about 90% of the deaths from malaria. The other four parasites are P. vivax, P. malariae, P. ovale and P. knowlesi. 2 This study was carried out in the Netherlands under close medical supervision. 3 This period was considered to be a sufficient one for chloroquine levels to drop below that which might inhibit parasite multiplication and malaria development. exposed to infected mosquitoes and tested for protection against P. falciparum. The scientists found that all the human subjects in the vaccine group had acquired complete protection against the parasite while the subjects in the control group who did not receive immunisation developed parasitemia4. This unique method of immunisation5 allowed the human immune system to direct its response to eliminating the P. falciparum parasite at the earlier, liver stage of its life cycle, as chloroquine would kill it at the later blood stage. The method used malaria parasites that were whole and intact to induce an immune response as opposed to other methods that included the use of genetically inactivated parasites or parasites that had been weakened by radiation to induce anti-malaria immunity. The experimental results demonstrated a significant improvement over other experimental malaria vaccines currently used in clinical trials that could induce up to Prof Renia, Principal Investigator at SIgN, who had played a pivotal role in this project by conceptualising the experimental protocol, as well as designing and conducting the follow-up experiments, said, “It is not practical to apply the experimental method used in our study as a means of vaccination. But, this method of immunisation could be applied successfully to similar investigations to find biological markers which would indicate the extent of protection against malaria. It would thus advance the currently limited knowledge of what constitutes protective Using their novel approach, the scientists examined and gained important insight into the protective anti-malaria immune response in humans, which was difficult to acquire, whether through previous exposure6 or vaccination. By studying the antibodies, biological substances and cells present in the human subjects from the time of pre- to post-immunisation, the scientists identified a specialised group of parasite-specific immune cells which indicated protection against P. falciparum in 4 Parasitemia is a condition where parasites are found in the blood of subjects. 5 The details of the experiment are published in the 30 July issue of the New England Journal of Medicine. 6 Naturally acquired immunity to malaria develops over a period of 10-20 years and with repeated exposure to malaria parasites in the field. humans. These cells, known as pluripotent effector memory T cells7, were found in the blood samples of subjects who had been immunised and re-exposed to P. falciparum, but were not found in the subjects in the control group. Hence, the specialised cells could serve as a biological indicator to check for malaria protection in humans during the stages of vaccine development. Associate Professor Raymond Lin, Senior Consultant and Head of Microbiology at the Department of Laboratory Medicine, National University Hospital, said, “This is an elegant study which uses nature itself to tell us the answer to some basic questions regarding what can induce protective immunity against malaria. It shows that exposure to whole unmodified malarial parasites can protect against subsequent infection, while minimizing adverse events through the use of anti- malarial drugs. This provides hope for future vaccines and offers prospects of alternatives to conventional vaccine approaches. Also, the remarkable experiment studies infection in humans, using real parasites and real mosquitoes yet in a controlled and safe clinical trial setting. Future vaccine researchers will doubtless refer to this paper for guidance. Malaria is a major health threat in this region which Singaporeans are vulnerable to, so having world-class malaria expertise here is Prof Renia 8 joined SIgN in 2007 to lead the Laboratory of Malaria Immunobiology. In addition to the Netherlands and France, Prof Renia also works closely with scientists and physicians from hospitals and centres conducting malaria studies in countries such as Thailand, where malaria is still a burden to public health authorities. The exchange of knowledge and resources between the collaborating parties entails the following – Prof Renia’s laboratory in SIgN offers immunological expertise on the study of malaria parasites while the partnering Thai centres, financed by the Wellcome Trust, provide data derived from biochemical and drug testing on patient samples. Prof Renia and his lab members also travel to the field site at the border of Thailand and Myanmar, from where they work in close proximity 7 Pluripotent effector memory T cells are immune cells that can mediate the removal of pathogens from the human body. 8 Before joining A*STAR’s Singapore Immunology Network, Prof Renia was research director at the French National of Institute of Health (INSERM), and also held appointments as co-director and director of the Department of Immunology at the Institut Cochin in Paris from 2001 to 2006. to the patients to conduct follow-up experiments to better understand the molecular AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH (A*STAR)
For queries and further clarification, please contact: Wang Yunshi (Ms) Corporate Communications Agency for Science, Technology and Research (A*STAR) Tel: (65) 6826 6443 Email: Notes to the Editor
The research findings described in the press release can be found in the following
article, “Protection against a malaria challenge by sporozoite inoculation”, published
in the 30 July 2009 issue of New England Journal of Medicine.
Authors: M. Roestenberg1*, M. McCall1*, J. Hopman1, J. Wiersma1, A.J.F. Luty1, GJ
van Gemert1, M. van de Vegte-Bolmer1, B. van Schaijk1, K. Teelen1, T. Arens1, L.
Spaarman1, Q. de Mast2, W. Roeffen1, G. Snounou3,4, L. Rénia5, A. van der Ven2, C.
Hermsen1 and R. Sauerwein1#
Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, INSERM Unité 511, Département de Parasitologie, Hôpital Pitié-Salpêtrière, 75013 Paris, Université Pierre et Marie Curie, 75005, Paris Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science, These authors contributed equally to this work. Corresponding author: Prof. Dr. Robert W. Sauerwein, email:
About the Singapore Immunology Network (SIgN)
SIgN, officially inaugurated on 15 January 2008, is a research consortium under
A*STAR's Biomedical Research Council. It is aimed at building on the strengths of
the existing immunology research groups at A*STAR, as well as expanding and
strengthening the immunology research expertise in Singapore. SIgN's objectives
include coordinating basic, translational and clinical research needed to establish
immunology as a core capability in Singapore. The major focus areas of research at
SIgN are Infection and Inflammation, in which SIgN researchers investigate immune
responses and regulation in disease-specific contexts. Through this, SIgN aims to
build up 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 initiatives within Biopolis and across Singapore, as well as
to obtain international recognition as a leading immunology research hub while
establishing relationships with the best institutions in the world.
For more information about SIgN, please visit
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
Singapore. A*STAR actively nurtures public sector research and development in
Biomedical Sciences, and Physical Sciences and Engineering, and supports
Singapore's key economic clusters by providing intellectual, human and industrial
capital to our partners in industry and the healthcare sector. It oversees 23 research
institutes, consortia and centres located in Biopolis and Fusionopolis, and the area in
their vicinity, and supports extramural research in the universities, hospitals,
research centres, and with other local and international partners.
For more information about A*STAR, please visit


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