Malaria is responsible for over 2 million deaths each year. The development of an efficient vaccine would present by far the best solution for solving this disastrous situation. Liver-Stage-Antigen-3 (LSA-3) is an antigen that is mainly exhibited by Plasmodium falciparum sporozoites and liver-stage parasites. It is characterized by its remarkable antigenicity in humans with a wide range and a variety of B and T-lymphocyte epitopes, by its extremely high immunogenicity and by an excellent protective efficacy against sporozoite challenge in animal models. Therefore, PfLSA-3-rec is a promising candidate vaccine against P. falciparum in humans The aim is to screen two different formulations of the recombinant malaria vaccine PfLSA-3-rec, one adjuvated with aluminium hydroxide and one with Montanide Isa 720, by assessing the safety and immunogenicity (phase I) profile of each formulation in humans, as well as its protective efficacy following a sporozoite challenge (phase IIa).

(Main) Inclusion Criteria:

• Male and female age ≥18 and ≤ 45 years
• Good general health based on history, physical en laboratory examination
• Available for and willingness to undergo a P. falciparum sporozoite challenge following the immunization course
• Resident near the Radboud University Medical Center Nijmegen, having 24h access to a telephone
• Living with a third party that could contact the clinicians in case of alteration of conscience
• Agreement to refrain from blood donation during the course of the study and afterwards
• Negative pregnancy test and the use of effective contraception during the whole study period

(Main) Exclusion Criteria:

• Any history of malaria
• Known exposure to malaria in the previous 6 months, defined as a visit to a malaria-endemic region.
• Planned to travel to endemic malaria areas during the study period
• Prior administration of an investigational malaria vaccine
• Administration of a vaccine or gammaglobulin not foreseen by the clinical trial protocol within 30 days prior to the first immunization and up to six months after the last immunization.
• Participation in any other clinical trial within 90 days prior to the onset of the trial or more than four clinical trials in the past year
• The use of chronic immunosuppressive drugs or other immune modifying drugs within three months of vaccination (inhaled and topical corticosteroids are allowed)
• Positive serological tests for P falciparum (LSA-3) ELISA and/or a positive P. falciparum PCR
• Known hypersensitivity to vaccine components
• Contra-indications to Riamet® including treatment taken by the volunteers that interfere with Riamet® (e.g. concurrent use of medicines that prolong QT-interval)
• 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
• An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system.