A Trial For The Study of Falciparum Malaria Protein 014 Administered Via Intramuscular Injection in Healthy Adults

Inclusion Criteria:

1. Healthy adults between the ages 18-55 (inclusive);
2. Able and willing to provide written, informed consent;
3. Able and willing to comply with all research requirements, in the opinion of theInvestigator;
4. Agreement to refrain from blood donation during the course of the study. Volunteerswho have undergone CHMI can donate to other research once the study is complete butcannot donate to the American Red Cross for at least 3 years after the CHMI event;
5. Laboratory Criteria within 90 days before enrollment:

• Hemoglobin ≥ 11.7 g/dL for women; ≥ 12.0 g/dL for men;
• White Blood Cell count = 3,800-10,800 cells/mm3;
• Platelets = 140,000-400,000/mm3;
• Alanine aminotransferase (ALT; SGPT) 9-46 U/L male and 6-29 U/L female;
• Serum creatinine ≤ 1.5 mg/dL;
• Negative HIV testing (HIV Ab / antigen 4th generation screen with reflexconfirmatory RNA testing);
• Negative hepatitis B surface antigen (HBsAg) and hepatitis C antibody testing;Note: As above, Grade 1 lab abnormalities detected on screening may be repeatedat PI discretion. Persistent Grade 1 abnormalities that are felt to represent thenon-pathologic baseline for the subject will be discussed with the researchmonitor and documented before a subject is enrolled in the trial, and areallowable per discretion and agreement of the PI and Research Monitor

6. Birth control requirements: Female subjects must meet one of the following 2 criteria:

• No reproductive potential due to post-menopausal status (12 months of natural [spontaneous] amenorrhea) or hysterectomy, bilateral oophorectomy or tuballigation;
• Women of childbearing potential should agree to practice highly effectivecontraception at least 30 days before enrollment and through 3 months post-CHMIor post-last vaccination (whichever is latest), using one of the followingmethods: condoms (male or female) with spermicide; diaphragm, or cervical capwith spermicide; intrauterine device; contraceptive pills, patch, injection,intravaginal ring or other FDA-approved contraceptive method; male partner haspreviously undergone a vasectomy; abstinence. Male subjects are encouraged but not required to practice highly effectivecontraception to avoid pregnancy in their partner from 30 days prior to enrollmentthrough 60 days post-CHMI. This is due to the potential impact of malaria andantimalarial medications on spermatogenesis.

7. For all female subjects except those with a history of hysterectomy or bilateraloophorectomy, a negative β-HCG pregnancy test (urine) on day of enrollment, each dayof vaccination, and the day of CHMI (tubal ligations have a not insignificant failurerate, 12 months of spontaneous amenorrhea does not completely preclude pregnancy andcan be a result of polycystic ovarian syndrome);
8. Reachable (24/7) by mobile phone or other method of communication (email, landline,etc) during the period between CHMI and 28 days post-CHMI, per volunteer report;
9. No plans to travel outside the Washington DC metro area (DC, Maryland, and Virginia)between the day of challenge and 28 days post-challenge; For Travel outside the USoccurring 28 days post-challenge to a malaria endemic area inclusion will be at thediscretion of the PI.
10. If a subject is active duty military, he or she must obtain approval from his or hersupervisor per WRAIR Policy 11-45;
11. Must have low (< 10%) cardiac risk factors according to clinical Gaziano (NHANES I)criteria assessed at screening, and a normal or normal variant ECG;
12. Completion of Study Comprehension Quiz (minimum passing score of 80% with 2 attemptspermitted).
13. Subject must be willing to take anti-malarial treatment after CHMI;
14. Subject must provide 2 emergency contacts who will be made aware of the subject'sparticipation in this trial and the vital importance of being reached during thechallenge phase of the study. Both contacts must be verified by pone prior to subjectenrollment. Verification will be define as either speaking to the emergency contact over the phone,hearing their name included in the voicemail response, or confirming the emergency contactuses the number if a third party answers the phone.

Exclusion Criteria:

1. History of malaria infection (any species) or residence in a malaria-endemic area formore than 5 years (includes previous participation in CHMI studies).
2. Previous travel to malaria endemic regions within the past 6 months before studyenrollment defined as first vaccination or day of challenge (for infectivity controls)or planned travel to malaria endemic regions during the vaccination, CHMI and 28-dayCHMI follow-up period; For Travel outside the US occurring 28 days post-challenge to amalaria endemic area exclusion will be at the discretion of the PI.
3. Any history of receiving a malaria vaccine.
4. Received an investigational product in the 30 days before enrollment, or planned toreceive during the study period.
5. Concurrent participation in another clinical research study.
6. Any use of medications that prevent or treat malaria during the 1 month prior tochallenge or planned use during the study (outside of the drugs provided by the studyteam).
7. Any serious medical illness or condition involving the heart, liver, lungs, orkidneys.
8. Any significant risk for developing heart disease in the next 5 years, assessedaccording to clinical Gaziano (NHANES I) criteria assessed at screening, and an ECG.
9. Receipt of immunoglobulins or blood products within 3 months before enrollment.
10. Any history of anaphylaxis.
11. History of sickle cell trait or disease, or any condition that could affectsusceptibility to malaria infection, per subject verbal report.
12. Pregnancy, lactation, or intention to become pregnant during the study, and 3 monthsafter malaria challenge, if applicable.
13. Contraindications or allergies to the use of all 3 proposed anti-malarial medications;Malarone (atovaquone/proguanil), Coartem (artemether/lumefantrine) and chloroquine;contraindication to 1 or 2 is not exclusionary.
14. History of active/recent cancer still within treatment or active surveillancefollow-up (except basal cell carcinoma of the skin and cervical carcinoma in situ).Treated/resolved cancers with no likelihood of recurrence may be deemed acceptable atPrincipal investigator discretion
15. History of autoimmune disease.
16. Significant (eg systemic anaphylaxis) hypersensitivity reactions to mosquito bites (local reactions at the site of mosquito bites are not an exclusion criterion)requiring hospitalization.
17. Suspected or known current alcohol or drug abuse as defined by an alcohol intake ofgreater than 3 drinks a day on average for a man, and greater than 2 drinks a day onaverage for a woman.
18. Any other significant disease, disorder or finding which may significantly increasethe risk to the volunteer because of participation in the study, affect the ability ofthe volunteer to give informed consent, participate in the study, or impairinterpretation of the study data, in the opinion of the Investigator.
19. Current anti-tuberculosis prophylaxis or treatment.
20. History of splenectomy.
21. History of confirmed or suspected immunodeficiency.
22. History of Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic formsof angioedema.
23. History of Asthma that is unstable or required emergent care, urgent care,hospitalization or intubation during the past 2 years.
24. History of Diabetes mellitus (type I or II), with the exception of gestationaldiabetes.
25. History of Thyroid disease (except for well controlled hypothyroidism).
26. History of Idiopathic urticaria within the past year.
27. History of hypertension that is not well controlled by medication or that ispersistently greater than 150/95 at screening...
28. History of bleeding disorder diagnosed by a doctor (eg, factor deficiency,coagulopathy, or platelet disorder requiring special precautions) or significantbruising or bleeding difficulties with IM injections or blood draws.
29. History of chronic or active neurologic disease to include seizure disorder andchronic migraine headaches. Exceptions are: i) childhood febrile seizures, or ii)seizures secondary to alcohol withdrawal more than 3 years ago.
30. Subjects receiving any of the following substances:

• Systemic immunosuppressive medications or cytotoxic medications within 12 weeksbefore enrollment [with the exception of a short course of corticosteroids (≤ 14days duration or a single injection) for a self-limited condition at least 2weeks before enrollment; inhaled, intranasal or topical steroids are notconsidered exclusionary]
• Treatment with known immunomodulators (other than nonsteroidal anti-inflammatorydrugs [NSAIDs]) for any reason.
• History of receipt of medication that prevent or treat malaria within 1 month ofCHMI
• Live attenuated vaccines within 30 days before initial study vaccineadministration
• Medically indicated subunit or killed vaccines, eg, influenza, pneumococcal, orallergy treatment with antigen injections, planned for administration 14 daysbefore or after study vaccine administration

31. History of arthritis diagnosis other than osteoarthritis.
32. History of other diagnosed rheumatoid disorders.
33. Any history of psoriasis (itchy skin rash) or porphyria (rare disturbance ofmetabolism), since these conditions could get worse after treatment with chloroquine (a medication for treating malaria).
34. Subject must not have a fever in order to receive the study vaccine or participate inthe malaria challenge.