Malaria vaccine could target variant parasite proteins

23 November 2012

Anopheles gambiae mosquito

Image: Anopheles gambiae mosquito©  US Centers for Disease Control and Prevention.

A major survey of variations in malaria genes has identified potential targets for a vaccine against the disease.

Malaria is one of the most devastating diseases in the developing world but there is currently no vaccine for it. "An effective and cheap vaccine would be a very valuable public health tool," said Tony Holder, of the MRC's National Institute for Medical Research (now part of the Francis Crick Institute), who took part in the research.

Malaria is caused by five species of protozoan parasites called Plasmodium. These parasites are spread to people through the bites of infected mosquitoes. The parasites have antigens - proteins - on their surfaces that evoke immune responses in infected people.

A person with 'acquired immunity' to an infection has been previously exposed to that infection (either naturally or by a vaccine) and their body has developed defences against it. This acquired immunity means that the next time they encounter the same infection, their body will already be prepared to fight it off.

"In the case of malaria, acquired immunity is against certain parasite antigens but not others," said Dr Holder.

Variations in the genes for antigens such as those on the malaria parasites occur naturally and are known as polymorphisms. However certain malaria genes have higher-than-usual levels of such polymorphisms. This is because people in malaria-prevalent areas have acquired immunity to different versions of the antigens, subjecting them to something known as selection pressure.

"This acquired immunity drives the selection of new antigen variants that can side-step a person's protective response. A protective immune response to the new variant then develops, driving selection of yet another variant," Dr Holder explained.

Dr Holder and his colleague Ellen Knűpfer in the Division of Parasitology collaborated with colleagues at the London School of Hygiene and Tropical Medicine, the Wellcome Trust Sanger Institute, the University of Oxford and the MRC in The Gambia.

The scientists carried out a comprehensive screen to find antigen variants that are targets of acquired immunity (and could therefore also be targeted by a potential vaccine). To do this they compared the antigen sequences from parasites isolated from 65 infected people in The Gambia. This is the largest sample of parasite genomes from a single location reported to date.

As expected, they found a number of genes with high levels of polymorphic variation, which could be future candidates for studies of immune mechanisms and potential vaccine development.

Tony Holder said: "The search for antigens to form the basis of a vaccine against malaria and to prevent the disease has proved difficult. This genetic approach identifies those proteins that are most variable and potentially under strong selection pressure from host immunity. The next challenges will be to show a direct role of these proteins in a part of the malaria disease process, such as invasion of red blood cells, and to prove that specific antibodies can inhibit this process."

He added: "There is a caveat - an effective vaccine based on one of these proteins would itself drive further evolution in the parasite to escape the vaccine-induced immunity. But we should be able to think of ways to overcome that too."

The article, Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites, was published recently in PLOS Genetics.

  • National Institute of Medical Research scientists took part in a comprehensive survey of malaria parasite genes and found some that may be targets for future vaccine research.
  • They focused on antigens - proteins on the parasite that cause immune responses in victims - with high levels of variation due to selection pressure from natural immunity in the population, which may also be good targets for a vaccine.
  • Malaria remains one of the most devastating diseases in the developing world - one report showed it caused 1.2 million deaths in 2010 alone. In Africa, a child dies every minute from malaria. The most commonly used drugs are failing rapidly due to resistance, alternatives are expensive and there is no vaccine.