A Study to Assess the Immunogenicity, Tolerability and Safety of a Malaria Vaccine and Also Its Protective Efficacy in a Malaria Challenge Model

Inclusion Criteria: * Healthy male or non-pregnant female subjects aged ≥18 to ≤50 years on Study Day 0. * Able and willing to participate for the duration of the study, to comply with protocol provisions and to undergo malaria challenge. * Able and willing to provide written informed consent. * Free of obvious health-problems as established by medical history, physical examination, laboratory assessment and clinical judgment of the investigator. * If the participant is biologically female she must: * Have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test performed at screening within 7 days before the 1st vaccine administration, and agree to a urine β-hCG pregnancy test at Study Day 0 and at each subsequent vaccine administration, before the challenge period, and at the end of the challenge period. * Agree to consistently use effective contraception from 21 days prior to Study Day 0 for the duration of the study, for sexual activity that could lead to pregnancy. * Agree to not seek pregnancy through alternative methods such as artificial insemination or in vitro fertilization until after the last scheduled protocol visit. * Male subjects engaged in sexual activities which could lead to pregnancy must agree to use a reliable barrier contraceptive plus spermicide for the duration of the study. Exclusion Criteria: * Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history that may have implications for current health status in the opinion of the Investigator. A clinically significant condition or process includes but is not limited to: * A process that would affect the immune response, * A process that would require medication that affects the immune response, * Any contraindication to repeated phlebotomy, * A condition or process in which signs or symptoms could be confused with reactions to vaccination or malaria challenge and/or infection, including dermatologic abnormalities at the site of sporozoite inoculation/vaccination, or * Any condition specifically listed among the exclusion criteria below. * Clinically significant acute illness, including oral temperature \>38.0 °C, or infection within 2 weeks of Study Day 0 that, in the opinion of the Investigator, would interfere with study assessments or cause significant implications for subject safety. * History of, or known active cardiac disease including: (1) prior myocardial infarction (heart attack); (2) angina pectoris; (3) congestive heart failure; (4) valvular heart disease; (5) cardiomyopathy; (6) pericarditis; (7) stroke or transient ischemic attack; (8) exertional chest pain or shortness of breath; or (9) other heart conditions under the care of a doctor. * Elevated (moderate or high) risk of coronary heart disease as determined by the NHANES I cardiovascular risk assessment criteria. * Clinically significant ECG findings, as determined by the study cardiologist. * History of malignancy, including hematologic and skin cancers (except for a localized basal cell carcinoma). * History of coagulation defects or bleeding that can not be linked to trauma or surgery. * History of receiving blood or blood products (such as blood transfusions, platelet transfusion, immunoglobulins, hyperimmune serum) within 6 months prior to Study Day 0. * History of mental illness as defined by symptoms interfering with social or occupational function or suicidal thoughts / attempts, excluding minor depression resolved or successfully treated at least 3 years prior to Study Day 0. * Any clinically significant history of known or suspected anaphylaxis or hypersensitivity reaction to vaccinations. * History of splenectomy. * Clinically significant screening laboratory abnormalities within 90 days of Study Day 0. * Positive serology for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B surface antigen (HBsAg). * Positive Neutralizing Antibody titers (IC90 \>16) against Ad26 and/or Ad35. * Pregnant or lactating female. * Chronic (longer than 14 days) administration of immunosuppressants (including oral or inhaled) or other immune-modifying drugs within 6 months prior to Study Day 0, including oral corticosteroids in dosages of ≥0.5 mg/kg/day prednisone or equivalent. * Blood donation (typical US blood volume donations are 470 mL) or significant blood loss (defined as total cumulative volume \>500 mL, including screening blood volumes) within 56 days before first dosing or plasma donation within 7 days prior to Study Day 0. * Vaccination with a live vaccine within 30 days prior to Study Day 0 or with a non-replicating, inactivated or subunit vaccine within 14 days prior to Study Day 0 or planned vaccination of any type during the study period. * Prior receipt of a malaria vaccine. * Any history of malaria diagnosed on positive blood smear. * Use of antimalarial prophylaxis, or travel to a malaria endemic region within 6 months prior to Study Day 0. * Any history of residence (\>3 months) in area known to have significant transmission of Plasmodium falciparum. * Planned travel to a malaria endemic region during the study period. * Prior receipt of a recombinant adenovirus vector vaccine. * Known hypersensitivity to components of the vaccine or proposed antimalarial medications. * Employee at the malaria clinical trial center or investigator or relative children or spouse of any investigator. * Identification of any condition or finding that, in the opinion of the investigator, would interfere with or serve as a contraindication to protocol adherence, assessment of study endpoints or would jeopardize the rights, safety or welfare of the subject participating in the study. * Smokers with current use of \>10 cigarettes/day or \>15 pack-years of lifetime cigarette use. * Known history of hemoglobinopathy. * Suspected or known alcohol or drug abuse as defined by the American Psychiatric Association in the DSM IV. * Ocular disease defined as retinopathy or visual field defects. * Chronic neurological symptoms including seizures or migraine headaches. * Concurrent participation in other investigational protocols or in receipt of an investigational product within the previous 6 months of Study Day 0 or planned receipt of another investigational product during the course of the study.