Public Release:  New malaria vaccine candidates identified

Previously untested antigens found in large-scale study of patients in Kenya

Wellcome Trust Sanger Institute

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IMAGE: Children and guardians present to a local dispensary for sampling for the detection of anti-malarial antibodies. view more

Credit: Juliana Wambua

Researchers have discovered new vaccine targets that could help in the battle against malaria. Taking a new, large-scale approach to this search, researchers tested a library of proteins from the Plasmodium falciparum parasite with antibodies produced by the immune systems of a group of infected children.

The tests measured which proteins the children's immune systems responded to, revealing antigens that had not previously been identified as possible vaccine targets and new insights into the ways antigens could be used in combination to increase protection.

"Resistance to malaria drugs is an increasing problem so vaccines are desperately needed to battle the Plasmodium falciparum parasite before it has a chance to make people sick," says Dr Faith Osier, first author from the Kenya Medical Research Institute. "This study presents us with a large number of new vaccine candidates that offer real hope for the future."

A group of children infected with malaria were followed over a six-month period by scientists at the Kenya Medical Research Institute (KEMRI). While some patients became sick, others were protected by naturally occurring antibodies that stopped the malaria parasite from penetrating their red blood cells during the blood stage of the disease, which produces severe symptoms such as fever and anaemia. Researchers used samples taken from these children to identify combinations of antibodies that provided up to 100 per cent protection against clinical episodes of malaria.

The study used a library of parasite proteins that was generated using an approach developed at the Wellcome Trust Sanger Institute by Dr Gavin Wright and Dr Julian Rayner. These researchers had previously developed a new approach to express large panels of correctly folded, full-length proteins from the Plasmodium falciparum parasite, targeting proteins involved in the invasion of human red blood cells. In this study, Sanger Institute scientists collaborated with colleagues in Kenya to see which of them the children's immune systems had developed antibodies against.

"The use of these proteins by the Sanger Institute's Malaria Programme is helping to zero in on and exploit the weakest point in the malaria parasite's life cycle," says Dr Julian Rayner, an author from the Sanger Institute. "Trials for vaccines in the past have focussed on one target at a time and have had limited success; with this approach, we can systematically test larger numbers of targets and identify targets that might work in combination."

The findings of this research add further weight to the theory that a successful blood-stage vaccine needs to target multiple antigens. The next step in this research will be to generate antibodies against all of the proteins in the library and test them in the laboratory in different combinations to see whether combinations that appear to protect individuals in the field are able to directly prevent parasite invasion. Such studies are now underway at the Sanger Institute. At KEMRI, Dr Faith Osier's team is working on validating these findings in other African countries.

"Each year, hundreds of thousands of people die from malaria; but hundreds of millions are infected, many of whom are protected from severe symptoms by their immune response," says Dr Kevin Marsh, Director of the KEMRI Wellcome Trust Research Programme at the Kenya Medical Research Institute. "Collaborating with our colleagues at the Sanger Institute helps to bring the latest technological advances to the field, which in this case has highlighted combinations of naturally occurring antibodies that could contribute to the design of new vaccines."

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Notes to Editors

Publication Details

Osier, F et al. (2014) New antigens for a multicomponent blood-stage malaria vaccine. Science Translational Medicine. DOI: 10.1126/scitranslmed.3008705

Funding

Supported by the Wellcome Trust, UK (grant number 098051 to the Sanger Institute; grant numbers 092741 and 077176 to the Immunology Programme at Kenya Medical Research Institute Centre for Geographical Medicine Research, Coast (KEMRI-CGMRC); grant numbers 089833 and 088634 to F.H.O and M.J.M respectively; and grant number 077092 to KEMRI-CGMRC) and the Medical Research Council UK (grant number MR/J002283/1 to J.C.R and G.K.W).

Participating Centres

Please see the paper for a full list of participating centres.

Selected Websites

The Kenya Medical Research Institute (KEMRI) is a state corporation established through the Science and Technology (Amendment) Act of 1979, as the national body responsible for carrying out health research in Kenya. Since its inception, KEMRI has developed a critical mass of scientists and technical personnel, to enable it mount a competitive research infrastructure to rank as a leading centre of excellence in health research both in Africa as well as globally.

http://www.kemri.org

The Medical Research Council has been at the forefront of scientific discovery to improve human health for more than a century. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers' money in some of the best medical research in the world across every area of health. Twenty-nine MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms.

http://www.mrc.ac.uk/

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.

http://www.sanger.ac.uk

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.

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