Dose Escalation PfSPZ-CVac

Exclusion Criteria

• •Currently is breast-feeding (if female).
• •Pregnancy as determined by a positive urine or serum human choriogonadotropin (beta- hCG) test at any point during the study (if female).
• •Recent travel to a malaria endemic area within 5 years of enrollment (Endemic areas are defined per the CDC website. Factors such as but not limited to use of antimalaria prophylaxis during travel, length of stay, activities during the travel, history of illnesses within 30 days of travel will be considered to determine the likelihood that the subject was exposed to malaria)
• •Planned travel to a malaria endemic area (as defined by the Center for Disease Control) during the study period
• •Reported history of confirmed malaria diagnosis on peripheral blood smear or by clinical history in the past 10 years.
• •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)
• •Abnormal urinalysis as defined by positive urine glucose, protein, and red blood cells. Subject can be included if investigator determine the abnormality is not clinically significant .
• •BMI \< 17 or BMI \> 35
• •Anticipated use during the study period, or use within the following periods prior to enrollment:
• •* Investigational malaria vaccine within the last five years
• •* Malaria chemoprophylaxis within 6 months
• •* 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.
• •* Blood products or immunoglobulins within 6 months
• •* Systemic antibiotics with antimalarial effects within 30 days (such as clindamycin, doxycycline)
• •* Investigational or non-registered product or vaccine within 30 days
• •* Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to Sanaria PfSPZ Challenge
• •* Medications known to interact with pyrimethamine and/or chloroquine (for the main and pilot study participants ONLY), atovaquone, proguanil (ALL participants)
• •Reported history of:
• •* Sickle cell disease, sickle cell trait, or other hemoglobinopathies
• •* Splenectomy or functional asplenia
• •* Systemic anaphylaxis
• •* Any allergic reactions to study drugs (pyrimethamine, chloroquine) or NSAIDs, atovaquone, proguanil
• •* Documented history of chronic or active neurologic disease (including seizures, uncontrolled migraine headaches)
• •* Psoriasis or porphyria
• •* Ocular diseases including retinopathy or visual field defects
• •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:
• •* A process that would affect the immune response, or requires medication that affects the immune response
• •* Any contraindication to repeated phlebotomy
• •* 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
• •* A chronic or subclinical condition which could be exacerbated by administration of any of the PfSPZ-CVac components or malaria infection
• •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
• •Clinically significant ECG findings, as determined by the expert study cardiologist
• •Moderate or high risk for coronary heart disease (CHD) based on NHANES I cardiovascular risk assessment
• •Acute illness at the time of enrollment
• •Infection with HIV, Hepatitis B, Hepatitis C
• •Psychiatric condition that precludes compliance with the protocol including but not limited to:
• •* Psychosis within the past 3 years
• •* Ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years
• •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
• •Clinical trial staff and/or Sanaria Inc. employees with direct involvement in the conduct of the trial are excluded from participation.
• •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.
• •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.