02:00pm Wednesday 16 October 2019

New candidate malaria vaccine neutralises parasite strains

Schizont of Plasmodium falciparumAccording to the ‘World Malaria Report 2010’, malaria killed an estimated 781 000 people in 2009, mainly young children and pregnant women. It is caused by parasites that are injected into the bloodstream by infected mosquitoes. The most deadly species, Plasmodium falciparum, is responsible for nine out of ten deaths from malaria. Vaccination is likely to be the most cost-effective way of protecting people from malaria; however, no licensed vaccine is currently available. One vaccine is achieving promising but incomplete levels of protection in clinical trials in Africa, but scientists believe a new and more effective vaccine will be required to eradicate the disease.

In early November, research published in the journal ‘Nature’ showed that the P. falciparum parasite relies on a single receptor, known as ‘basigin’, on the surface of red blood cells to invade the cell. The parasite attaches a protein – the antigen RH5 – to the receptor, in a sense ‘unlocking’ the doorway for the parasite to enter the red blood cell. Once there, it grows and replicates, causing potentially life-threatening disease.

Today, in a paper published in the journal ‘Nature Communications’, a team of scientists from the Jenner Institute at the University of Oxford led by Dr Simon Draper, working with colleagues from the Wellcome Trust Sanger Institute and the Kenya Medical Research Institute-Wellcome Trust Research Programme in Kilifi, Kenya, demonstrate that a vaccine they have developed induces an antibody response in animal models that is capable of neutralising all the tested strains of the P. falciparum parasite.

“Our initial finding, reported last month, was unexpected and completely changed the way in which we view how the malaria parasite invades red blood cells,” says Dr Gavin Wright from the Wellcome Trust Sanger Institute, a co-author on both studies. “It revealed what we think is the parasite’s Achilles’ heel in the way it invades our cells and provided a target for potential new vaccines.”

Dr Sandy Douglas, a Wellcome Trust Clinical Research Training Fellow from the University of Oxford and first author on the new study, adds: “We have created a vaccine that confirms the recent discovery relating to the biology of RH5, given it can generate an immune response in animal models capable of neutralising many – and potentially all – strains of the P. falciparum parasite, the deadliest species of malaria parasite. This is an important step towards developing a much-needed vaccine against one of the world’s major killers.”

The antigens of the malaria parasite can be genetically very diverse, as the parasite is forced to evolve to stay one step ahead of the immune system and avoid recognition by antibodies. However, the RH5 antigen appears to have little genetic diversity. The researchers believe that this is because even people who have been naturally and repeatedly exposed to malaria have low or undetectable levels of antibodies that target this particular antigen; these very low levels of antibody would be insufficient to kill the parasites, and so would not exert a selective pressure for the antigen to evolve variability.

Professor Adrian Hill, a Wellcome Trust Senior Investigator at the University of Oxford, says: “Vaccines against malaria are notoriously difficult to develop because the parasites’ antigens – the target of vaccines – tend to be genetically so diverse. The RH5 antigen doesn’t show this diversity, making it a particularly good target for a vaccine to exploit. Our next step will be to begin safety tests of this vaccine. If these prove successful, we could see clinical trials in patients beginning within the next two to three years.”

The Jenner Institute is funded through a Strategic Award from the Wellcome Trust, whose goals include combating infectious diseases.

Image: A schizont of Plasmodium falciparum, form a bone marrow smear. Credit: Liverpool School of Tropical Medicine courtesy of A Stich/Wellcome Images


Craig Brierley
Senior Media Officer
Wellcome Trust
+44 (0)20 7611 7329

Notes for editors

New research paper:
Douglas AD et al. The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody. Nature Communications 20 December 2011 [epub].

November research paper:
Crosnier C et al. Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum. Nature 9 November 2011 [epub].

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

About the University of Oxford Medical Sciences Division
The University of Oxford’s Medical Sciences Division is recognised internationally for its outstanding research and teaching, attracting the brightest minds from all over the world.

It is one of the largest biomedical research centres in Europe, with over 2500 people involved in research and more than 2800 students, and brings in around two-thirds of the University’s external research income. Listed by itself, that would make it the fifth largest university in the UK in terms of research grants and contracts.

Oxford is home to the UK’s top-ranked medical school, and partnerships with the local NHS Trusts enable patients to benefit from the close links between medical research and healthcare delivery.

14 winners of the Nobel Prize for Physiology or Medicine worked or were educated at Oxford, and the Division is home to 29 Fellows of the Royal Society and 68 Fellows of the Academy of Medical Sciences.

The development of penicillin at Oxford ushered in the modern age of antibiotics, and the confirmation of the link between smoking and cancer has prevented many millions of deaths. Oxford continues to be at the forefront of medical research, whether it’s the genetic and molecular basis of disease, the latest advances in neuroscience, or clinical studies in cancer, diabetes, heart disease and stroke. Oxford has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic.

A great strength of Oxford medicine is its longstanding network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.

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