Scientists at the Medical Research Council's National Institute for Medical Research (NIMR; now part of the Francis Crick Institute) have unexpectedly discovered that protective immunity to malaria is not necessarily specific to one lifecycle stage of the parasite.
The research changes how we think about malaria immunity and opens up new avenues for vaccine research.
The study was carried out by Wiebke Nahrendorf in Jean Langhorne's laboratory at NIMR. She explained: "Protection against malaria can be achieved by repeatedly exposing human volunteers to the bites of mosquitoes infected with the malaria parasite, Plasmodium, while treating them with the antimalarial drug chloroquine. This is known as 'chemoprophylaxis and sporozoites' (CPS).
"Chloroquine does not interfere with the normal development of malaria parasites in the skin and liver and only targets the parasites once they reach the bloodstream. It is therefore unclear in this immunisation regimen which lifecycle stage is the source and target of antimalarial immunity."
To investigate, the researchers worked with Robert Sauerwein from Radboud University Medical Center in Nijmegen, The Netherlands. Together they developed a new mouse model of CPS immunisation. They immunised mice using a protocol similar to that used for human CPS vaccination, using mosquitoes infected with a malaria parasite that infects mice, and then treated the mice with chloroquine. It is assumed that his type of immunisation induces immunity specifically against parasites that develop in the liver from the injected sporozoites.
However, with the low doses of sporozoites injected by the mosquito in this model, the researchers found that there was no immunity against liver-stage parasites. Instead, immunity only occurred when very large numbers of sporozoites were injected directly into the bloodstream.
The fact that immunity against liver-stage parasites is only acquired after injection of high doses of sporozoites may explain why there is little evidence of immunity against this stage of infection in areas where malaria occurs naturally and why people get repeatedly infected by mosquito bites.
Although CPS immunisation does not protect against the liver stage of the infection, the very short exposure to blood-stage parasites during the immunisation process does induce immunity to blood-stage malaria parasites. Importantly a blood-stage infection induces protective immunity against both blood and stage liver-stages. These results demonstrate for the first time that immunity to malaria is not necessarily specific for a particular life-cycle stage. Instead antigens, which are shared between the different life-cycle stages of the malaria parasite mediate cross-stage immunity.
Dr Langhorne said: "The existence of strong protection against multiple stages of the malaria parasite will redefine how we think about immunity to this complex parasitic disease and will open up new avenues for developing multi-stage malaria vaccines."
The paper, Blood-stage immunity to Plasmodium chabaudi malaria following chemoprophylaxis and sporozoite immunization, is published ineLife.
