Sanaria PfSPZ Challenge With Pyrimethamine Chemoprophylaxis (PfSPZ-CVac Approach): Phase 1 Trial to Determine Safety and Protective Efficacy of Sanaria PfSPZ Challenge With Concurrent Pyrimethamine Treatment That Inhibits Development of Asexual B...

* INCLUSION CRITERIA: All of the following criteria must be fulfilled for a subject to participate in this trial: 1. Age greater than or equal to 18 and less than or equal to 50 years. 2. In good general health and without clinically significant medical history 3. Malaria comprehension exam completed, passed (a score of greater than or equal to 80% or per investigator s discretion) and reviewed prior to enrollment 4. Reliable access to the clinical trial center and availability to participate for duration of study 5. Females of childbearing potential must be willing to use reliable contraception (as defined below) from 21 days prior to study day -2 to 28 days following last Sanaria . * Subject to the judgment and discretion of the PI, female participants who meet ANY ONE of the criteria listed immediately below, may not be required to take any additional measures to avoid pregnancy. Such participants will be counseled on risks at the time of consent and at appropriate points (e.g. when pregnancy testing occurs) during the study: * Females who have had their uterus, and/or BOTH ovaries removed * Females who have had BOTH fallopian tubes surgically tied or removed * Females who are above the age of 45 and have spontaneously had no menses at any point during the past 12 or more consecutive months (i.e. have reached menopause) * Females who, in the conservative and reasonable judgment of the PI (e.g. due to sexual orientation or serious life choice (such as being celibate clergy or transgender), during the entire trial will NOT participate in any potentially reproductive sexual contact * Females who, in the conservative and reasonable judgment of the PI, are in a monogamous stable relationship with a male who has undergone vasectomy at least 4 months prior or another procedure/medical condition that deems the male sterile * Subject to the judgment and discretion of the PI, female participants who DO NOT meet ANY of the criteria listed above, will be appropriately counseled on reproductive risks and pregnancy avoidance, and will be required to adhere to the following measures and agree to 2 methods of pregnancy prevention as noted below: CATEGORY 1: * a highly effective hormonal method to prevent pregnancy \[e.g. CONSISTENT, CONTINUOUS use of contraceptive pill, patch, ring, implant or injection\], and/or * IUD or equivalent IN ADDITION TO CATEGORY 2: -a barrier method to be used at the time of potentially reproductive sexual activity (e.g. \[male/female condom, 'cap,' or diaphragm\] plus spermicide). EXCLUSION CRITERIA: A subject will be excluded from participating in this trial if any one of the following criteria is fulfilled: 1. Currently is breast-feeding (if female). 2. Pregnancy as determined by a positive urine or serum human choriogonadotropin (beta-hCG) test at any point during the study (if female). 3. Recent travel to a malaria endemic area within 5 years of enrollment 4. Planned travel to a malaria endemic area during the study period 5. History of confirmed malaria diagnosis on peripheral blood smear or by clinical history in the past 10 years. 6. Hemoglobin, WBC, platelets, ALT, and creatinine outside of local lab normal range (subjects may be included at the investigator s discretion for not clinically significant values outside of normal range) 7. Abnormal urinalysis as defined by positive urine glucose, protein, and hemoglobin. Subject can be included if investigator determine the abnormality is not clinically significant . 8. Anticipated use during the study period, or use within the following periods prior to enrollment: 1. Investigational malaria vaccine within the last five years 2. Malaria chemoprophylaxis within 6 months 3. Chronic systemic immunosuppressive medications (\>14 days) within 6 months (e.g.cytotoxic medications, oral/parental corticosteroids \>0.5 mg/kg/day prednisone or equivalent). Corticosteroid nasal spray for allergic rhinitis and topical corticosteroids for mild, uncomplicated dermatitis are allowed. 4. Blood products or immunoglobulins within 6 months 5. Systemic antibiotics with antimalarial effects within 30 days (such as clindamycin, doxycycline) 6. Investigational or non-registered product or vaccine within 30 days 7. Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to Sanaria PfSPZ Challenge 8. Medications known to interact with pyrimethamine, chloroquine, atovaquone, proguanil (during the study period only) 9. History of: 1. Sickle cell disease, sickle cell trait, or other hemoglobinopathies 2. Splenectomy or functional asplenia 3. Systemic anaphylaxis 4. Any allergic reactions to study drugs 5. Documented history of chronic or active neurologic disease (including seizures, uncontrolled migraine headaches) 6. Psoriasis or porphyria 7. Ocular diseases including retinopathy or visual field defects 10. Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history that may have clinically significant implications for current health status and participation in the study in the opinion of the Investigator. A clinically significant condition or process includes but is not limited to: 1. A process that would affect the immune response, or requires medication that affects the immune response 2. Any contraindication to repeated phlebotomy 3. A condition or process in which signs or symptoms could be confused with reactions to malaria challenge and/or infection, including dermatologic abnormalities at the site of sporozoite inoculation 4. A chronic or subclinical condition which could be exacerbated by administration of any of the PfSPZ-CVac components or malaria infection 11. Weight \> 77.2 Kg at the time of screening (this will result in a minimum dose of pyrimethamine of approximately 0.7mg/Kg for a 50mg daily dose). (Note not required for Arm 4 CHMI controls) 12. History of, or known active cardiac disease including: (1) prior myocardial infarction (heart attack); (2) angina pectoris; (3) congestive heart failure; (4) valvular heart disease; (5) cardiomyopathy; (6) pericarditis; (7) stroke or transient ischemic attack; (8) exertional chest pain or shortness of breath; or ( 9) other heart conditions under the care of a doctor 13. Clinically significant ECG findings, as determined by the expert study cardiologist 14. Moderate or high risk for coronary heart disease (CHD) based on NHANES I cardiovascular risk assessment 15. Acute illness at the time of enrollment 16. Infection with HIV, Hepatitis B, Hepatitis C 17. Psychiatric condition that precludes compliance with the protocol including but not limited to: 1. Psychosis within the past 3 years 2. Ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years 18. Suspected or known current alcohol or drug abuse as defined by the American Psychiatric Association in the DSM V at the discretion of the PI 19. Clinical trial staff and/or Sanaria employees with direct involvement in the conduct of the trial are excluded from participation. 20. Participating in other clinical trials involving investigational interventions or off label medication use during the study period (excluding participation in the optional long term follow up visits). Participation in other trials such as observational or imaging studies will be discussed with the investigators. 21. Any other finding that, in the judgment of the Investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a subject s ability to give informed consent, or increase the risk of having an adverse outcome from participating in the study