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.