Inclusion Criteria:
1. Healthy males and females, based on clinical and laboratory findings (note: an effort will be made to recruit roughly equal numbers of males and females, although a balanced sex ratio is not required)
2. From 18 to 50 years of age
3. Adults with a Body Mass Index (BMI) 18 to 30 Kg/m\^2
4. Residence in the study area for the duration of the study
5. Agreement to release medical information and to inform the study doctor concerning contraindications for participation in the study
6. Willingness to be attended to by a study clinician and take all necessary medications prescribed during study period
7. Agreement to provide contact information of a third-party household member or close friend to study team
8. Agreement not to participate in another clinical trial during the study period
9. Agreement not to donate blood during the study period (until final clearance is completed)
10. Able and willing to complete the study visit schedule over the study follow up period
11. Willingness to undergo HIV, hepatitis B (HBV), hepatitis C (HCV), and sickle cell testing
12. Able to demonstrate their understanding of the study by responding correctly to 18 out of 20 true/false statements (in a maximum of two repeat attempts for those who failed to pass in the first attempt)
13. Signed written informed consent, in accordance with local practice
14. Has not been treated with any antimalarial medication for at least two weeks before the initial clearance treatment.
15. Female volunteers must be non-pregnant (as demonstrated by a negative urine pregnancy test) and provide consent / assent of their willingness to take protocol-defined measures not to become pregnant during the study and safety follow-up period. Acceptable measures to not become pregnant include oral or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner, or sterile sexual partner during the entire study. Women with a history of surgical or chemical sterilization (e.g., tubal ligation, hysterectomy, other) must provide written documentation of the procedure from a health care provider.
16. Ability to complete pre-vaccination drug clearance without significant untoward effects.
Exclusion Criteria:
1. Unable to provide informed consent including inability to pass the test of understanding
2. Receipt of a malaria vaccine in a prior clinical trial
3. History of a splenectomy or sickle cell disease.
4. History of a neurologic disorder (including non-febrile seizures or complex febrile seizures) or formal history of migraine headache
5. Current use of systemic immunosuppressant pharmacotherapy
6. Receipt of a live vaccine within 4 weeks of first immunization or of 3 or more non-live vaccines within 2 weeks of first immunization
7. Women who are breast-feeding, pregnant or planning to become pregnant during the study period
8. Known allergy to artemether-lumefantrine (AL), dihydroartemisinin-piperaquine (DHA-P), or any component of the investigational products
9. History of anaphylaxis or other life-threatening reaction to a vaccine
10. Participation in any study involving investigational vaccine or drug within 4 weeks before enrollment that in the estimation of the site PI might adversely affect the individual's safety or the quality of data to be collected
11. Evidence of increased cardiovascular disease risk; defined as \>10% five-year risk by non-laboratory method
12. Plan to participate in another investigational vaccine/drug research during the study
13. Plan for major surgery between enrollment until last study visit
14. Use or planned use of any drug with anti-malarial activity that would precede or coincide with vaccination through to 56 days after controlled human malaria infection (CHMI)
15. Anticipated use of medications known to cause drug interactions with DHA-P (antiarrhythmics, neuroleptics, macrolide antibiotics, fluoroquinolones, imidazole and triazole antifungal agents, quinine, halofantrine, pentamidine and saquinavir, certain non-sedating antihistamines, all of which can affect QT intervals ) or AL (the same list of drugs affecting QT intervals plus rifampin, carbamazepine, phenytoin, St. John's wort and antiretroviral drugs)
16. Positive HIV, HBsAg or HCV serology
17. Positive sickle cell trait or disease testing
18. History of or evidence for other chronic disease conditions including cancer, diabetes, renal failure, hypertension, and tuberculosis
19. History of arrythmias or cardiac disease, or an abnormal electrocardiogram, defined as one showing prolonged QT interval, pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm including isolated premature ventricular contractions, but excluding isolated premature atrial contractions; right or left bundle branch block; or advanced (secondary or tertiary) A-V heart block; or other clinically significant abnormalities on the electrocardiogram
20. Any clinically significant deviation from the normal range in biochemistry or hematology tests measured at screening and not resolving (grade 1 abnormalities are allowed)
21. Any medical, psychiatric, social, behavioral or occupational condition or situation (including active alcohol or drug abuse affecting social function) that, in the judgment of the site PI, impairs the participant's ability to give informed consent, increases the risk to the participant of participation in the study, affects the ability of the participant to participate fully in the study, or might negatively impact the quality, consistency, integrity or interpretation of data derived from their participation in the study
22. Inability to complete a course of malaria treatment before receipt of investigational product
