Phase I/II Trial of a Malaria Vaccine in Adults Living in the United States of America

- Controlled challenge, Phase I/IIa WRAIR study.

- Healthy, malaria-naive adults aged 18 - 50 years.

- 2 groups, 5 subjects in group A (10µg dose) and 15 subjects in group B (50µg dose).

- Control: none for immunization phase; infectivity controls for challenge and rechallenge
phases. Six infectivity controls per day of challenge will be enrolled for the challenge
phases, with 3 alternates available for challenge if needed.

- Vaccination schedule of 0, 1 months.

- Challenge of up to 15 subjects in Group B.

- Contingent upon short term efficacy, rechallenge of initially protected subjects 6
months (+/- 2 months) after second dose of vaccine.

- Self-contained study.

- Duration of the study, per subject: approximately 15 months (screening, enrollment,
vaccination, challenge and rechallenge).

- Data collection will be by done at the site.

Inclusion Criteria:

- A male or non-pregnant female 18 to 50 years of age (inclusive) at the time of
screening.

- Written informed consent obtained from the subject before screening procedures.

- Free of obvious health problems as established by medical history and clinical
examination before entering into the study.*

- Available to participate for duration of study (approximately 15 months).

- If the subject is female, she must be currently using birth control, must be
surgically sterilized, or must be at least 1-year post menopausal.

- Pass a comprehension assessment test.

Exclusion Criteria:

- Prior receipt of an investigational malaria vaccine.

- Use of any investigational or non-registered drug or vaccine other than the study
vaccine(s) within 28 days preceding the first dose of study vaccine, or planned use
during the study period.

- Administration of chronic immunosuppressants or other immune modifying drugs within
six months of vaccination.

- Chronic use of antibiotics with anti-malarial effects.

- Planned administration/ administration of a vaccine not foreseen by the study protocol
within 30 days of the first dose of vaccine(s).

- History of use of anti-malarial medication within 60 days prior to vaccination.

- Any history of malaria.

- Known exposure to malaria within the previous 12 months.

- Planned travel to malarious areas during the study period.

- Any confirmed or suspected immunosuppressive or immunodeficient condition, including
HIV infection.

- A family history of congenital or hereditary immunodeficiency.

- History of allergic disease or reactions likely to be exacerbated by any component of
the vaccine.

- Chronic or active neurologic disease including seizures, but not including a single
febrile seizure as a child.

- History of splenectomy.

- Acute disease at the time of enrollment.

- Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal
functional abnormality, as determined by physical examination or laboratory screening
tests.

- Personal history of autoimmune disease or subjects who describe a first-degree
relative with clearly documented autoimmune disease.

- Seropositive for hepatitis B surface antigen.

- Seropositive for Hepatitis C virus (antibodies to HCV).

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

- Pregnant or lactating female.

- Suspected or known current alcohol abuse as defined by the American Psychiatric
Association in DSM IV.

- Chronic or active intravenous drug use.

- History of severe reactions to mosquito bites as defined as anaphylaxis.

- Female who intends to become pregnant during the study.

- Any history of anaphylaxis in reaction to vaccination.

- A clinical history of sickle cell disease or sickle cell trait.

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