Sanaria PfSPZ Challenge With Pyrimethamine or Chloroquine Chemoprophylaxis Vaccination (PfSPZ-CVac Approach): A Randomized Double Blind Placebo Controlled Phase I/II Trial to Determine Safety and Protective Efficacy Against Natural Plasmodium Falcipa...

* INCLUSION CRITERIA: * Age greater than or equal to 18 and less than or equal to 50 years (for booster phase, age greater than or equal to 18 and less than or equal to 52 years) * Resident of Bancoumana or nearby areas * In good general health and without clinically significant medical history * Malaria comprehension exam completed, passed (a score of greater than or equal to 80% or per investigator s discretion) and reviewed prior to enrollment * Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process * Willing to have blood samples stored for future research * Available for the duration of the study * Females of childbearing potential must be willing to use reliable contraception (as defined below) from 21 days prior to first PfSPZ Challenge injection to 28 days following last PfSPZ Challenge exposure (or equivalent study day for Arm 5 controls). For the booster phase, this applies from 21 days prior to the booster vaccination to 28 days post booster vaccination. * Reliable methods of birth control include one of the following: confirmed pharmacologic contraceptives (parenteral) delivery; intrauterine or implantable device. OR * Reliable methods of birth control include concurrent use of a pharmacologic and a barrier method, i.e., two of the following: confirmed pharmacologic contraceptives (oral, transdermal) delivery or vaginal ring AND condoms with spermicide or diaphragm with spermicide. OR * Non-childbearing women will also be required to report date of last menstrual period, history of surgical sterility (i.e. tubal ligation, hysterectomy) or premature ovarian insufficiency (POI), and will have urine or serum pregnancy test performed per protocol. * For booster phase only: previously or currently enrolled in protocol #19-I-N099 and completed all three primary vaccinations. EXCLUSION CRITERIA: * Pregnancy, as determined by a positive urine or serum human choriogonadotropin (beta-hCG) test (if female) --NOTE: Pregnancy is also a criterion for discontinuation of any further dosing or non-safety related interventions for that subject. * Currently breast-feeding (if female) * Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and comply with the study protocol * Hemoglobin, WBC, absolute neutrophils, and platelets outside the local laboratorydefined limits of normal (subjects may be included at the investigator s discretion for 'not clinically significant' values) * Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratoryMali PfSPZ-CVac (pyrimethamine) defined upper limit of normal (subjects may be included at the investigator s discretion for not clinically significant values) * Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B (HBV) (For the booster phase: re-testing NOT required for enrollment unless clinically indicated) * Known or documented sickle cell disease by history (Note: known sickle cell trait is NOT exclusionary) * Clinically significant abnormal electrocardiogram (ECG) (For the booster phase: re-testing NOT required for enrollment unless clinically indicated) * Moderate or high risk for coronary heart disease (CHD) based on NHANES I cardiovascular risk assessment * Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis * History of receiving any other investigational product within the past 30 days * Participation or planned participation in a clinical trial with an investigational product prior to completion of the last required protocol follow-up visit * Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months. * History of a severe allergic reaction or anaphylaxis * Severe asthma (defined as asthma that is unstable or required emergent care,urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years) * Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sj(SqrRoot)(Delta)gren s syndrome, or autoimmune thrombocytopenia * Known immunodeficiency syndrome * Known asplenia or functional asplenia * Use of: * a. Chronic (greater than or equal to 14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone \>10 mg/day) or immunosuppressive drugs within 30 days of vaccination * b. Antimalarials for example artemether, artemether-lumefantrine, artesunate, artesunate-amodiaquine, other than those prescribed by the investigator as part of the study procedures within 14 days prior to the first vaccine * c. Systemic antibiotics with known antimalarial activity such as trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, ciprofloxacin or azithromycin within 5 half-lives of the drug prior to the first vaccine * Receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks prior to Vaccination #1 and every subsequent vaccination day * Receipt of immunoglobulins and/or blood products within the past 6 months * Previous receipt of an investigational anti-infectivity malaria vaccine in the last 2 years (this requirement is waived for the booster phase) * Known allergies or contraindication against: PYR, chloroquine, NSAIDs, artemether, lumefantrine * Other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of a participant participating in the trial, interfere with the evaluation of the study objectives, or would render the subject unable to comply with the protocol.