The objective of the study is to induce a protective immune response against malaria in healthy human volunteers. The different parts of the immune response will then be studied.

Efforts to develop vaccines against malaria still represent a substantial focus of current research activities. Factors that have hampered the development of a subunit vaccine include the complexity of the malaria life cycle, the wide variety of immune response induced by the malaria parasite, and an incomplete knowledge of protective immunity. This study is therefore aimed at inducing protective immunity against malaria in 15 healthy volunteers. Volunteers will be exposed to the bites of infectious mosquitoes 3 times with live P. falciparum sporozoites under chloroquine prophylaxis. Challenge with infected mosquitoes will be given after stopping chloroquine prophylaxis.

Five volunteers will form a control group; they will be exposed to non-infectious mosquitoes under chloroquine prophylaxis.

Endpoints include the time and height of parasitemia after challenge, the development of fever and immunological parameters.

Inclusion Criteria:

• Age > 18 and < 45 years healthy volunteers (males or females).
• General good health based on history and clinical examination.
• All volunteers have to sign the informed consent form.
• Negative pregnancy test.
• Use of adequate contraception for females
• Reachable by phone during the whole study period.
• Volunteer agrees to inform the general practitioner and agrees to sign a request for medical information concerning contra-indications for participation in the trial

Exclusion Criteria:

• History of malaria or residence in malaria endemic areas within the past six months.
• Positive serology for P. falciparum
• Previously participated in any malaria vaccine study
• Symptoms, physical signs and laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the study results or compromise the health of the volunteers.
• Cardiovascular risk >10% according to European guidelines, taking into account sex, age, cholesterol, weight, smoking habits, blood pressure, diabetes
• Any laboratory abnormalities on screened blood samples beyond the normal range, as defined at UMC St Radboud. Positive HIV, HBV or HCV tests.
• Volunteers should not be enrolled in any other clinical trial during the whole trial period.
• Volunteers should not receive chronic medication, especially immunosuppressive agents (steroids, immunomodulating or immunosuppressive drugs) during the three months preceding the screening visit or during the study period.
• Pregnant or lactating women.
• Volunteers unable to give written informed consent.
• Volunteers unable to be closely followed for social, geographic or psychological reasons.
• Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study.
• Known hypersensitivity for anti-malaria drugs
• Volunteers are not allowed to travel to malaria endemic countries during the study period.