Sequential Optimization of Dose and Schedule of PfSPZ Vaccine

Inclusion Criteria: * Healthy adults aged 18 to 45 years * Able and willing (in the Investigator's opinion) to comply with all study requirements * Willing to allow the investigators to discuss the volunteer's medical history with their general practitioner ('Hausarzt' in German) if required * Residence in Tübingen or surroundings for the period of the trial * Women only: Must agree to practice continuous effective contraception for the duration of the study (a method which results in a failure rate less than 1% per year) * Agreement to refrain from blood donation during the course of the study and after the end of their involvement in the study according to the local and national blood banking eligibility criteria (currently there is a four year restriction in Germany) * Written informed consent to receive PfSPZ products: * Optimization phase: PfSPZ Vaccine for immunization and PfSPZ Challenge (NF54) for CHMI * PfSPZ Challenge (7G8) dose finding: PfSPZ Challenge (7G8) for CHMI * Verification phase: PfSPZ Vaccine for immunization, PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8) for CHMI * Reachable (24/7) by mobile phone during the immunization and CHMI period * Willingness to take a curative antimalarial regimen following CHMI * Agreement to stay overnight for observation during the period of intensive follow-up post-challenge if required * Answer all questions on the informed consent quiz correctly * A body mass index \<35 Exclusion Criteria: * History of P. falciparum malaria * Planned travel to malaria endemic areas before end of CHMI (28 days after CHMI) * Use of systemic antibiotics with known antimalarial activity within 30 days of study enrollment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin) * Receipt of an investigational product in the 30 days preceding enrollment, or planned receipt during the study period * Prior receipt of a malaria vaccine * Immunization with more than three other vaccines within the past four weeks * HIV infection * Any confirmed or suspected immunosuppressive or immunodeficient state, asplenia, recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed) * Use of immunoglobulins or blood products within 3 months prior to enrolment * Known or suspected hemolytic disease or presence of hemoglobinopathies * Pregnancy, lactation or intention to become pregnant during the study * Contraindications to the use of the following antimalarial medications: atovaquoneproguanil, artemether-lumefantrine or mefloquine * History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ) * History of serious psychiatric condition that may affect participation in the study (including but not restricted to organic, including symptomatic, mental disorders \[ICD-10 code: F00-F09\], schizophrenia, schizotypal and delusional disorders \[F20-F29\], mood (affective) disorders \[F30-F39\], mental retardation \[F70-F79\], Disorders of psychological development \[F80-F89\] or any other psychiatric condition that required hospitalization or psychiatric treatment over an extended period). * Any other serious chronic illness requiring hospital specialist supervision * Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 60 g (men) or 40 g (women) per day or a carbohydrate deficient transferrin (CDT) level ≥2.5% * Suspected or known injecting drug abuse in the 5 years preceding enrollment * Positive for hepatitis B surface antigen (HBs-antigen) * Seropositive for hepatitis C virus (antibodies to HCV) * Falling in moderate risk or higher categories for fatal or non-fatal cardiovascular event within 5 years (\>10%) determined by non-invasive criteria for cardiac risk * Abnormal electrocardiogram on screening: pathologic Q wave and significant ST-T wave changes, left ventricular hypertrophy, clinically significant arrhythmias, left bundle branch block, secondary or tertiary A-V heart block * A QT/QTcB interval \>450 ms * Volunteers unable to be closely followed for social, geographic or psychological reasons * Any clinically significant abnormal finding on biochemistry or hematology blood tests, urine analysis or clinical examination * History of seizure (except isolated and uncomplicated febrile convulsion at childhood) * Any other significant disease, disorder or finding which, in the opinion of the investigator, may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data