Safety and Protective Efficacy of Pb(PfCS@UIS4)

Inclusion Criteria

• Subject is aged ≥ 18 and ≤ 35 years and in good health.
• Subject has adequate understanding of the procedures of the study and is able and willing (in the investigator's opinion) to comply with all study requirements.
• Subject is willing to complete an informed consent questionnaire and is able to answer all questions correctly.
• Subject is able to communicate well with the investigator and is available to attend all study visits, lives in Rotterdam or in proximity to the trial centre (can be on site within 1 hour) or is willing to stay in a hotel close to the trial centre during part of the study (phase 1: from day of immunization to day 12 post-immunization; phase 2: from day of immunization to day 8 post-immunization.
• The subject will remain within the Netherlands from day -1 until day +28 after immunization during phase 1; from day -1 until day 12 after each immunization during phase 2, and during the challenge period, will not travel to a malaria-endemic area during the study period, and is reachable (24/7) by mobile telephone throughout the entire study period.
• Subject agrees to their general practitioner being informed and contacted about their participation in the study and agrees to sign a form to request the release by their General Practitioner (GP), and medical specialist when necessary, to the investigator(s), of any relevant medical information concerning possible contra-indications for participation in the study.
• The subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period and for a defined period thereafter according to current Sanquin guidelines (3 years minimum, depending on serology).
• For female subjects: subject agrees to use continuous adequate contraception** and not to breastfeed for the duration of study.
• Subject agrees to refrain from intensive physical exercise (disproportionate to the subject's usual daily activity or exercise routine) during the malaria challenge period.
• Subject agrees to avoid additional triggers that may cause elevations in liver enzymes including alcohol from baseline up to 1 week post treatment.
• Subject has signed written informed consent to participate in the trial.

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following.

1.1. Body weight 30 kg/m2 at screening. 1.2. A heightened risk of cardiovascular disease, as determined by: an estimated ten year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically significant arrhythmia's, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiac events in 1st or 2nd degree relatives <50 years old.

1.3. A medical history of functional asplenia, sickle cell trait/disease, thalassaemia trait/disease or G6PD-deficiency.

1.4. History of epilepsy in the period of five years prior to study onset, even if no longer on medication.

1.5. Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) 1.6. Chronic use of i) immunosuppressive drugs, ii) antibiotics, iii) or other immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use o