Phase 1 Clinical Trial With Controlled Human Malaria Infection (CHMI) to Evaluate the Safety and Efficacy of the Plasmodium Falciparum Vaccine Candidate FMP012 Administered Intramuscularly With AS01B Adjuvant System in Healthy Malaria-Naïve Adults

Inclusion Criteria:

- Healthy adults (male or non-pregnant, non-lactating female) 18 to 50 years of age
(inclusive) at the time of screening

- If the subject is female,

- Non-childbearing potential (ie, either surgically sterilized or one year
post-menopausal), abstinent or using adequate contraceptive precautions (eg,
intrauterine contraceptive device; oral contraceptives; diaphragm or condom in
combination with contraceptive jelly, cream or foam; Norplant® or Depo-Provera®)
during this study and must agree to continue such precautions until three months
after challenge

- A negative pregnancy test at the time of enrollment

- Free of significant health problems as established by medical history, laboratory, and
clinical examination before entering the study

- Subjects must have low cardiac risk factors according to the National Health and
Nutrition Examination Survey (NHANES) I criteria, medical history and family history,
blood pressure measurements, and a normal or normal variant ECG

- Available to participate and reachable by phone for duration of study (approximately
8-14 months) and reachable by phone at the 6 month post Controlled Human Malaria
Infection (CMHI) follow-up

- No plans to travel to outside the Washington DC area between the day of challenge and
either completion of treatment course (post-challenge) or, if subject remains
uninfected, 28 days post-challenge

- No plans to travel to a malaria endemic area during the course of the study

- Written informed consent must be obtained from the subject before screening procedures
are performed

- Subjects must score at least 80% correct on a multiple-choice quiz that assesses their
understanding of this study

- If a subject is active duty military, he or she must obtain approval from his or her
supervisor per Walter Reed Army Institute of Rese (WRAIR) Policy 11-45

Exclusion Criteria:

- Any history of malaria infection

- History of travel to P falciparum endemic areas in the 3 months prior to day of first
vaccination (Vaccination Groups) or day of challenge (Infectivity Control Group)

- Any history of receiving a malaria vaccine

- Receipt of any licensed vaccine within 7 days prior to first vaccination (Note:
subjects are encouraged to get recommended licensed preventive vaccinations during the
course of the study but are requested to schedule any routine preventive vaccinations
for at least 7 days before or after a scheduled FMP012/AS01B vaccination day)

- History of receipt of malaria prophylaxis during the 2 months prior to day of first
vaccination (Vaccination Groups) or day of challenge (Infectivity Control Group)

- History of use of any antibiotics with significant antimalarial activity (examples
include tetracycline, doxycycline, clindamycin, azithromycin, and sulfa drugs) during
the course of the study period (period starting one month prior to challenge,
Infectivity Control Group)

- Use of any investigational or non-registered drug or vaccine within 30 days preceding
the first dose of study vaccine or planned use during the study period.

- Any history of allergic reaction or anaphylaxis to previous vaccination (Vaccination
Groups)

- Allergy to egg protein (Vaccination Groups)

- Pregnant (positive β-human chorionic gonadotropin test, β-HCG) or lactating female at
screening or plans to become pregnant or breastfeed from the time of enrollment until
three months after challenge

- Allergy to antimalarial drugs or use of medications known to interact with chloroquine
(CQ)

- Significant (eg, systemic) hypersensitivity reactions to mosquito bites (local
hypersensitivity reactions at the site of mosquito bites are not an exclusion
criterion)

- History of sickle cell disease

- History of psoriasis or porphyria

- History of splenectomy

- Any confirmed or suspected immunodeficiency, including HIV infection

- Administration of chronic (defined as more than 14 days) immunosuppressive drugs or
other immune-modifying drugs within 6 months of vaccination

- History of autoimmune disease

- Family history of congenital or hereditary immunodeficiency

- Acute or chronic, clinically significant, pulmonary, cardiovascular, endocrine,
hepatic, or renal functional abnormality, as determined by history, physical
examination, or laboratory evaluation

- Chronic or active neurologic disease including seizure disorder and chronic migraine
headaches

- Administration of immunoglobulins and/or any blood products within the three months
preceding the first dose of study vaccine or any planned administration during the
study period

- Any abnormal baseline laboratory screening tests to include:

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above normal
range,

- Creatinine above normal range,

- Hemoglobin out of normal range,

- Platelet count out of normal range, or

- Total white blood cell (WBC) count out of normal range

- Seropositive for HIV or Hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg)
positive

- Hepatomegaly, right upper quadrant abdominal pain or tenderness

- An abnormal baseline screening ECG suggestive of cardiac disease as determined by a
clinical investigator

- Suspected or known current alcohol or drug abuse as determined from the medical
history or by physical examination

- Any other significant finding that in the opinion of the PI would increase the risk of
having an adverse outcome from participating in this study