Most malaria vaccine candidates haven't been investigated

Researchers at the Walter and Eliza Hall Institute (WEHI) have found that a vast majority of candidate proteins that could be used to produce a vaccine against the blood-stage of malaria have not been thoroughly researched, and have called for more resources to be devoted to the effort of identifying these potential vaccine targets.

Dr James Beeson, Dr Freya Fowkes and Dr Jack Richards, from the WEHI’s Infection and Immunity division, conducted a systematic review and meta-analysis of prospective cohort studies that examined natural immune responses against the blood-stage of malaria and found that only six of 100 potential proteins have been studied in depth.

Malaria is an infection of the blood cells caused by the parasite, Plasmodium falciparum, which is transmitted by mosquitoes. To date, it has proven a difficult disease to treat or vaccinate against, says Dr Beeson.

"Malaria has evolved very successful strategies for evading the immune response," says Beeson. "It's been a cat and mouse game between the immune response and the malaria parasite, and it's been winning for the last several thousand years."

However, individuals exposed to the malaria parasite do gradually build up resistance to it as the immune system begins to produce antibodies that recognise antigens on the parasite's surface. It's hoped that a sufficient number of antigens could be included in a malaria vaccine to prime the immune system to defend itself against the malaria parasite on first contact.

A number of studies have taken place around the world - focussing on sub-Saharan Africa - that explore the link between these naturally-produced antibodies and resistance to malaria.

The paper, published today in PLoS Medicine, examined 33 of these studies where the incidence of malaria had been recorded over time in groups of people with natural antibodies to specific antigens found on the merozoite, which is the blood-stage of the parasite. The meta-analysis identified six proteins that appeared to lend an increased resistance to infection by the malaria parasite, each of which could prove a promising vaccine target.

However, there are dozens more proteins that the parasite employs that might also prove to be effective targets for a vaccine, but these are yet to be studied in depth. According to Beeson, this means the most effective vaccine targets may yet to be found.

The researchers also proposed a framework for future studies to improve the consistency of results that will foster easier comparisons between results. They also stress that more studies need to take place outside of Africa in order to gain a more diverse insight in to the immune response against the malaria parasite.