• INCLUSION CRITERIA:

All of the following criteria must be fulfilled for a volunteer to participate in this trial:

• Age between 18 and 50 years (US) or 18 and 45 years (Mali), inclusive
• Good general health as a result of review of medical history and/or clinical testing at the time of screening
• Available for the duration of the trial (52 weeks)
• Willingness to participate in the study as evidenced by signing the informed consent document, or by fingerprinting the consent document with the signature of a witness (Mali)
• Known resident of the village of Bancoumana (Mali)

EXCLUSION CRITERIA (US):

A volunteer will be excluded from participating in this trial if any one of the following criteria is fulfilled:

1. Pregnancy as determined by a positive urine or serum test at any point during the study for human choriogonadotropin (Beta-hCG) (if female).
2. Subject is unwilling to use reliable contraception methods for the period of at least 2 months prior to first vaccination to 3 months after last vaccination (if female). Reliable methods of birth control include: pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; surgical sterilization; vaginal ring; intrauterine device; abstinence; and post-menopause (if female).
3. Currently is lactating and breast-feeding (if female).
4. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the study protocol.
5. Neutropenia as defined by an absolute neutrophil count less than 1500/mm(3).
6. Alanine transaminase (ALT) level above the laboratory-defined upper limit of normal.
7. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
8. Other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant participating in the trial or would render the subject unable to comply with the protocol.
9. History of receiving any investigational product within the past 30 days.
10. Participant has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
11. History of a severe allergic reaction or anaphylaxis.

12. Severe asthma. This will be defined as:

    • Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past 2 years, or that requires the use of oral or parenteral corticosteroids
    • Clinically significant reactive airway disease that does not respond to bronchodilators
13. Positive ELISA and confirmatory Western blot tests for HIV-1.
14. Positive ELISA and confirmatory tests for hepatitis C virus (HCV).
15. Positive hepatitis B surface antigen (HBsAg) by ELISA.
16. Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, or autoimmune thrombocytopenia.
17. Known immunodeficiency syndrome.
18. Positive serum anti-dsDNA titer.
19. Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study.
20. Receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to entry into the study.
21. History of a surgical splenectomy.
22. Receipt of blood products within the past 6 months.
23. Previous receipt of an investigational malaria vaccine.
24. Receipt of antimalarial prophylaxis during the past 12 months, or receipt of chloroquine or related compounds (hydroxychloroquine, amodiaquine, or primaquine) in the 8 weeks prior to study entry.
25. Prior malaria infection by history.
26. Any medical, psychiatric, social, or occupational condition or other responsibility that, in the judgment of the Principal Investigator (PI), would interfere with the evaluation of study objectives.

EXCLUSION CRITERIA (MALI):

A volunteer will be excluded from participating in this trial if any one of the following criteria is fulfilled:

1. Pregnancy as determined by a positive urine (Beta-hCG test at any point during the study (if female).
2. If female, subject and her spouse have not used or are unwilling to use reliable contraceptive methods such as: abstinence, birth control pills or birth control patches or vaginal ring, diaphragm with spermicide, IUD (intrauterine device), condom with spermicide, progestin implant or injection, or surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation) prior to enrollment to 3 months after the final vaccination. (At the time of vaccination, a female subject must have had a negative urine pregnancy test on 2 occasions at least 2 weeks apart, and must have used a reliable contraceptive method in the interim.)
3. Currently is lactating and breast-feeding (if female).
4. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, chronic infectious or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
5. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the study protocol.
6. Pre-existing known autoimmune diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia.
7. Laboratory evidence of possible autoimmune disease determined by anti-dsDNA titer that equals or exceeds 25 IU.
8. Laboratory evidence of liver disease (alanine aminotransferase (ALT) greater than 1.25 times the upper limit of normal of the testing laboratory).
9. Laboratory evidence of renal disease (serum creatinine greater than the upper limit of normal of the testing laboratory, or more than trace protein or blood on urine dipstick testing confirmed by repeat testing of clean-catch, midstream sample). (More than trace blood on urine dipstick will not exclude a female who is actively menstruating.)
10. Laboratory evidence of hematologic disease (absolute leukocyte count less than 3000/mm(3) or greater than 11,500/mm(3); hemoglobin less than 0.9 times the lower limit of normal of the testing laboratory, by gender; absolute granulocyte count less than 1300/mm(3); absolute lymphocyte count less than 1000/mm(3); or platelet count less than 110,000/mm(3)).
11. Other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol.
12. Participation in another investigational vaccine or drug trial within 30 days of starting this study, or while this study is ongoing.
13. Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
14. History of a severe allergic reaction or anaphylaxis.

15. Severe asthma. This will be defined as:

    • Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past 2 years, or that requires the use of oral or parenteral corticosteroids
    • Clinically significant reactive airway disease that does not respond to bronchodilators
16. Positive hepatitis B surface antigen (HBsAg). Hepatitis C antibody by rapid diagnostic test.
17. Known immunodeficiency syndrome.
18. Use of systemic corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study.
19. Receipt of a live vaccine within past 4 weeks or a non-live vaccine within past 2 weeks prior to entry into the study.
20. History of a surgical splenectomy.
21. Receipt of blood products within the past 6 months.
22. Previous receipt of an investigational malaria vaccine.
23. History of use of chloroquine or related compounds (hydroxychloroquine, amodiaquine, or primaquine) within 8 weeks of study entry.