Malaria is one of the most common tropical diseases, accounting for 228 million infections and 450.000 deaths each year. It is caused by five species of protozoan parasites belonging to the genus of the Plasmodia. Plasmodia have a complex life cycle: they are injected into the human host by female Anopheles mosquitos, migrate to the liver to replicate and then enter red blood cells. The typical symptoms of malaria with fever episodes are caused by the bursting of red blood cells, as the parasites leave to infect new cells.~The rising resistance of both parasites against anti-malarial drugs and mosquitoes against insecticides, make the need to eradicate malaria even more impellent. A promising approach to disease control is the development of an effective vaccine. Among the different approaches to vaccine development, live attenuated parasites stand out for their high protective efficacy (>90%).~The GA2 parasite, a new genetically attenuated malaria parasite, which is derived from the NF45 Plasmodium falciparum strain and has been engineered to arrest development in the liver before entering the bloodstream, was recently created. It should therefore not be able to cause malaria in humans. The idea is that the GA2 parasite will prime the immune system for recognition of non attenuated parasites in the future without causing disease itself. In other words, exposure to the innocuous GA2 parasite could confer protection against pathogenic malaria parasites.~Hence, this study is aimed at investigating the safety and tolerability of the GA2 parasite and at determining its potential protective efficacy against controlled human malaria infection. The former question will be investigated by exposing volunteers to sequentially increasing numbers of GA2-infected mosquito bites. The latter question will be investigated by repeatedly (3 times) exposing volunteers to the GA2 parasite and once to unattenuated parasites. The efficacy of the GA2 parasite will be compared to another genetically attenuated parasite, the GA1, which in previous studies has been shown to be safe and well-tolerated but only have limited protective efficacy. There will also be a placebo group.
This study will consist of two phases and be aimed at assessing the safety and tolerability of the new genetically attenuated GA2 malaria parasite (Phase 1) and its preliminary protective efficacy against controlled human malaria infection (Phase 2) in healthy Dutch volunteers.