A Challenge Study to Assess the Safety, Immunogenicity and Efficacy of a Malaria Vaccine Candidate

Inclusion Criteria: * Healthy adults aged 18 to 45 years. * Able and willing (in the Investigator's opinion) to comply with all study requirements. * Willing to allow the Investigators to discuss the volunteer's medical history with their General Practitioner (GP). * For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and vaccination, and on the day prior to blood-stage CHMI, and prior to the start of antimalarial treatment for Group 5 and 6 volunteers. * Agreement to refrain from blood donation during the course of the study. * Provide written informed consent. Additional Inclusion Criteria for Groups 5 - 6 * Agreement to permanently refrain from blood donation, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines. * Reachable (24 hours a day) by mobile phone during the period between CHMI and completion of antimalarial treatment. * Willingness to take a curative anti-malaria regimen following CHMI. * Answer all questions on the informed consent questionnaire correctly. Exclusion Criteria: * Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period. * Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data. * Any medical condition that in the judgment of the investigator would make intramuscular (IM) injection unsafe. * Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. * Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone 20 mg/day (for adult subjects), or equivalent. Inhaled and topical steroids are allowed. * Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab). * Chronic use of antibiotics with antimalarial effects (e.g. tetracyclines for dermatologic patients, sulfa for recurrent urinary tract infections, etc.). * History of malaria chemoprophylaxis within 60 days prior to vaccination. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. * Any history of anaphylaxis in relation to vaccination. * Pregnancy, lactation or willingness/intention to become pregnant during the study. * History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). * History of serious psychiatric condition likely to affect participation in the study. * Any other serious chronic illness requiring hospital specialist supervision. * Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week. * Suspected or known injecting drug abuse in the 5 years preceding enrolment. * Seropositive for hepatitis B surface antigen (HBsAg). * Seropositive for hepatitis C virus (antibodies to HCV). * History of clinical malaria (any species). * Travel to a malaria endemic region during the study period or within the previous six months. * Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis. * Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data. * Inability of the study team to contact the volunteer's GP to confirm medical history and safety to participate. Additional exclusion criteria for groups 5 - 6 * Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin). * History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection. * Use of medications known to cause prolongation of the QT interval AND existing contraindication to the use of Malarone. * Use of medications known to have a potentially clinically significant interaction with Riamet AND Malarone. * Contraindications to the use of all three proposed anti-malarial medications; Riamet, Malarone and Chloroquine. * Any clinical condition known to prolong the QT interval. * Family history of congenital QT prolongation or sudden death. * Positive family history in 1st and 2nd degree relatives \< 50 years old for cardiac disease. * History of cardiac arrhythmia, including clinically relevant bradycardia. * Volunteer unable to be closely followed for social, geographic or psychological reasons.