Advances in malaria vaccine development

Each year approximately 500,000 people die from malaria. Most are children. In fact, by the time you have finished reading this article, around three more people will have succumbed to this disease. On top of the cost measured in human life, there is also an economic cost, with some nations spending 1% of their GDP and up to 40% of their health budgets tackling malaria. Although there are antimalarial drugs available, there is a growing problem with the evolution of drug resistance. Therefore, given that vaccination is the most effective way of eradicating infectious diseases, an efficacious vaccine is imperative.

The development of such a vaccine has always been elusive, and Charles Laveran’s discovery that Plasmodium parasites cause malaria helps explain why. This difficulty is due to a number of factors which include the need for greater understanding of parasite biology and human immune response, and the immense complexity of the pathogen (there are numerous stages in the parasite’s life cycle, with differential gene regulation constantly changing potential targets). However, recent work by the Cowman lab and others has identified a protein complex, named PfRipr, on the outer tip of the blood stage of the parasite. This protein complex is essential for invasion of human red blood cells (the point of infection).

PfRipr makes an attractive vaccine target since its genetic disruption prevents parasitic development. Antibodies against it prevent parasite growth in the lab, and there is a correlation between people who have antibodies against PfRipr and the prevention of severe clinical malaria development. Dr. Christopher Haggarty-Weir’s research in Melbourne and Edinburgh involved producing various pieces of PfRipr in genetically engineered yeast so that the part of the protein inhibitory antibodies bound to could be ascertained, in addition to its structural determination. Knowing this allows vaccinologists to use an approach called ‘rational/structural vaccinology’ to develop an efficacious vaccine candidate for further studies. Dr. Haggarty-Weir’s work showed that out of the ten structured domains comprising the full-length PfRipr protein, domain 7 (termed EGF7) was where the inhibitory antibody bound to, inferring functional importance. One of the challenges faced was developing a clone of the bioengineered yeast that would produce the protein in significant quantities. This was overcome by screening numerous clones and developing an industrially-scalable method, using a fermenter in order to produce EGF5-7 in grams per litre quantities at a very low cost. The research also showed that EGF5-7 was stable in high temperatures (such as those found in Africa).

This work will allow scientists to further test this vaccine candidate in additional trials, with the knowledge that it can be produced affordably. This reduction in cost is a crucial step forward, due to the fact that malaria is endemic in regions of the world with higher poverty levels.

This article was written by Dr. Christopher Haggarty-Weir and edited by Sam Stanfield and James Hitchen.

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