Regimen Optimization Trial of PfSPZ Vaccine in Equatorial Guinea

Inclusion Criteria: 1. Healthy males and non-pregnant/non-lactating females, age 18 to 45 years at time of enrollment. 2. Provision of signed and dated informed consent form. 3. Demonstrate understanding of the study by responding correctly to 10 out of 10 true/false statements about the trial (a maximum of two additional attempts will be granted for those who fail to respond correctly to all true/false statements in their first attempt). 4. Stated availability and willingness to comply with all study procedures and visits for the duration of the trial, including the required vaccination and post-CHMI ward observation period. 5. Able to understand and communicate in Spanish, the national language of Equatorial Guinea 6. Be in good general health as evidenced by medical history, screening physical examination and laboratory findings. 7. Females of child bearing potential must agree to use injectable medroxyprogesterone for at least 4 weeks prior to enrollment and agree to continue to use medroxyprogesterone during the entire study period. 8. Female subjects must not be pregnant (as demonstrated by a negative urine pregnancy test) at enrollment and prior to each immunization. 9. Body Mass Index (BMI) of 18 to 30 kg/m2. 10. At least one year of residence on Bioko Island, Equatorial Guinea, and living close enough to Baney Clinical Research Center and Sampaka Hospital to be able to attend the required appointments at the study center. 11. Agree to release medical information and inform a study doctor about contraindications for participation in the study. 12. Willingness to be attended to by a study doctor and take all medications prescribed during the study period. 13. Agree to provide contact information of a third-party household member or close friend to the study team. 14. Agree not to participate in another clinical trial during the study period. 15. Agree not to donate blood during the study period. 16. Willing to undergo HIV, hepatitis B (HBV) and hepatitis C (HCV) tests. 17. Reachable by telephone for adverse event review. Exclusion Criteria: 1. Known allergic reactions to components of PfSPZ Vaccine, PfSPZ Challenge, or artemether-lumefantrine (AL). 2. Having received an investigational malaria vaccine in the last 5 years. 3. Having received any non-live vaccine in the 14 days prior to enrollment, any live vaccine in the 28 days prior to enrollment or three or more of any type of vaccine in the four months prior to enrollment. 4. Participation in any other clinical study involving investigational medicinal products including malaria drugs within 30 days prior to enrollment. 5. History of arrhythmias, prolonged QT-interval or other cardiac disease, or clinically significant abnormalities on electrocardiogram (ECG) at screening. 6. History of non-febrile seizures or complex febrile seizures. 7. History of cardiac disease in a 1st or 2nd degree relative when \<50 years of age. 8. A chronic illness including diabetes mellitus, cancer, HIV/AIDS, tuberculosis. 9. History of illicit drug or alcohol use that interferes with normal social function. 10. The use of chronic immunosuppressive drugs or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids are allowed) and during the study period. 11. Any clinically significant deviation from the normal range in biochemistry, hematology or urinalysis tests. 12. Positive HIV, hepatitis B virus or hepatitis C virus serologic tests. 13. Signs and symptoms of tuberculosis (e.g., chronic cough, night sweats, chronic fever, enlarged lymph nodes, unintended weight loss), or risk factors in an otherwise healthy person in combination with a positive tuberculin skin test (TST). 14. Symptoms, physical signs and/or laboratory values suggestive of systemic disorders including renal, hepatic, blood, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, and other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteer. 15. Any medical, psychiatric, social or occupational condition or situation that, in the judgment of the PI, impairs the volunteer's ability to give informed consent, increases the risk to the volunteer of participation in the study, affects the ability of the volunteer to participate fully in the study, or might negatively impact the quality, consistency or interpretation of data derived from their participation in the study.