Safety, Immunogenicity and Efficacy Against of a Combined Malaria Vaccine in Healthy Malaria-naïve Adults

Approximately 168 healthy, malaria-naïve volunteers aged 18 - 50 years, divided into 2 groups
(84 in each group), will receive either one dose of Ad35.CS.01 followed by two doses of
257049 at monthly intervals or 3 doses of 257049 vaccine at monthly intervals. Of these, a
maximum of 138 vaccinated volunteers will be challenged with P. falciparum infected
mosquitoes. The challenge will occur 2 weeks following the third immunization. A group of up
to 18 infectivity controls will begin participation in the study at the challenge stage.
These controls receive no vaccine and are enrolled for malaria-challenge only in order to
provide comparison group for vaccinated individuals.

Inclusion Criteria:

- Subjects who the investigator believes can and will comply with the requirements of
the protocol.

- A male or non-pregnant female 18 to 50 years of age at the time of first vaccination.

- 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 the duration of the study.

- Female subjects of non-childbearing potential.

- Female subjects of childbearing potential may be enrolled in the study, if the
subject:

- has practiced adequate Food and Drug Administration (FDA)-approved contraception
for 30 days prior to vaccination, and

- has a negative pregnancy test on the day of vaccination, and

- has agreed to continue adequate FDA-approved contraception during the entire
treatment period and for 2 months after completion of the vaccination series
and/or malaria challenge.

- Pass a comprehension assessment test.

Exclusion Criteria:

- Use of any investigational or non-registered product within 30 days preceding the
first dose of study vaccine, or planned use of any investigational or non-registered
product other than the study vaccines during the study period.

- Planned administration/ administration of a vaccine not foreseen by the study protocol
within 7 days of the first dose of vaccines.

- Prior receipt of an investigational malaria or adenovirus vaccine.

- Chronic use of antibiotics with antimalarial effects.

- History of malaria chemoprophylaxis within 60 days prior to vaccination.

- Any history of malaria.

- Planned travel to malaria endemic areas during the study period.

- History of allergic disease or reactions likely to be exacerbated by any component of
the vaccine(s) including latex.

- History of allergic disease or reactions likely to be exacerbated by chloroquine.

- History of psoriasis and porphyria, which may be exacerbated after chloroquine
treatment.

- Current use of medications known to cause drug reactions to chloroquine, such as
antacids and kaolin.

- Any history of anaphylaxis in reaction to any previous vaccination.

- History of severe reactions to mosquito bites.

- 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.

- Chronic administration of immunosuppressants or other immune modifying drugs within
six months prior to first vaccine dose.

- Any confirmed or suspected immunosuppressive or immunodeficient condition, including
immunodeficiency virus (HIV) infection.

- Family history of congenital or hereditary immunodeficiency.

- History of splenectomy.

- Major congenital defects or serious chronic illness.

- History of any neurological disorders or seizures.

- Acute disease and/or fever at the time of enrollment.

- Acute disease is defined as the presence of a moderate or severe illness with or
without fever. Subjects with a minor illness without fever may be enrolled at the
discretion of the investigator.

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

- Any abnormal baseline laboratory screening tests.

- Evidence of increased cardiovascular disease risk, "moderate" or "high", according to
the NHANES I criteria.

- An abnormal baseline screening electrocardiogram (EKG).

- Hepatomegaly, right upper quadrant abdominal pain or tenderness.

- Personal history of autoimmune disease.

- Seropositive for hepatitis B surface antigen or Hepatitis C virus (antibodies to HCV).

- Pregnant or lactating female.

- Female who intends to become pregnant during the study or planning to discontinue
contraceptive measures.

- Suspected or known current alcohol abuse.

- Chronic or active intravenous drug use.

- History of blood donation within 56 days preceding enrolment.

- 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.