Efficacy, Immunogenicity and Safety Study of GSK Biologicals' Candidate Malaria Vaccine Evaluating Different Dose Schedules in a Sporozoite Challenge Model in Healthy Malaria-naïve Adults

Protocol Amendment 1 incorporated: additional blood sampling for assessment of parasitemia
(polymerase chain reaction [PCR] testing); clarification that blood samples for both
peripheral blood mononuclear cells (PBMC) and plasma will be collected for repository
storage; revision of volume of whole blood samples to be taken for parasitemia assessment;
clarification that urine pregnancy tests will be conducted for all females and not just those
of childbearing potential; deletion of visit at Day 1 post day of challenge; clarification
that RNA sequencing and not deep sequencing will be performed in this study.

Inclusion Criteria:

- Subjects who, in the opinion of the investigator, can and will comply with the
requirements of the protocol.

- Written informed consent obtained from the subject prior to performing of any study
specific procedure.

- A male or female between, and including, 18 and 55 years of age at the time of
enrolment.

- Healthy subjects 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 may be enrolled in the study.

- Non-childbearing potential is defined as pre-menarche, current tubal ligation,
hysterectomy, ovariectomy or post-menopause.

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

- has practiced adequate contraception for 30 days prior to vaccination, and

- has a negative pregnancy test at enrolment, and

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

Exclusion Criteria:

- Use of any investigational or non-registered product (drug or vaccine) other than the
study vaccines during the period starting 30 days before the first dose of study
vaccines (Day -29 to Day 0), or planned use during the study period.

- Any medical condition that in the judgment of the investigator would make
intramuscular injection unsafe.

- Chronic administration of immunosuppressants or other immune-modifying drugs during
the period starting six months prior to the first vaccine dose. For corticosteroids,
this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are
allowed.

- Administration of long-acting immune-modifying drugs at any time during the study
period.

- Chronic use of antibiotics with antimalarial effects.

- Planned administration/administration of a vaccine not foreseen by the study protocol
in the period starting seven days before the first dose.

- Concurrently participating in another clinical study, at any time during the study
period, in which the subject has been or will be exposed to an investigational or a
non-investigational vaccine/product.

- Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).

- Documented HIV-positive subject.

- Previous vaccination against malaria.

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

- Any history of malaria (for the vaccine groups).

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

- History of splenectomy.

- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on
medical history and physical examination.

- Family history of congenital or hereditary immunodeficiency.

- History of any reaction or hypersensitivity likely to be exacerbated by any component
of the vaccine.

- History of anaphylaxis post-vaccination.

- Hypersensitivity to latex.

- History of any reaction or hypersensitivity 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.

- History of severe reactions to mosquito bites.

- Major congenital defects.

- Serious chronic illness.

- History of any neurological disorders or seizures.

- Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥
37.5°C/99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal
route.

- 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: alanine aminotransferase (ALT),
aspartate aminotransferase (AST), creatinine, hemoglobin, platelet count, total white
blood cells (WBC), out of normal range as defined in the protocol.

- Evidence of increased cardiovascular disease risk, "moderate" or "high", according to
the National health and nutrition examination survey I criteria.

- Hepatomegaly, right upper quadrant abdominal pain or tenderness.

- Personal history of autoimmune disease.

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

- Pregnant or lactating female.

- History of chronic alcohol consumption and/or drug abuse.

- Female planning to become pregnant or planning to discontinue contraceptive
precautions.

- 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.