A Study to Assess the Safety and Effectiveness of Two Experimental Malaria Vaccines

Inclusion Criteria: • Healthy adult 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 GP Participants of childbearing potential only: must practice continuous effective contraception for the duration of the study (see section 11.10) Agreement to refrain from blood donation for the duration of the study Able and willing to provide written informed consent to participate in the trial Additional inclusion criteria for groups 2 and 6: Negative haemoglobinopathy screen (including sickle cell disease and alpha and beta thalassaemia) and normal G6PD levels Agreement to permanently refrain from blood donation, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines (89) 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 Able to answer all questions on the informed consent questionnaire correctly at first or second attempt Able to travel to CCVTM without using public transport Exclusion Criteria: • History of clinical malaria (any species) or previous participation in any malaria (vaccine) trial or CHMI Travel to a clearly malaria endemic locality during the study period or within the preceding six months Use of immunoglobulins or blood products (e.g. blood transfusion) in the last three months Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days following each study vaccination, with the exception of COVID-19 vaccines, which should not be received between 14 days before to 7 days after any study vaccination Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period Concurrent involvement in another clinical trial involving an investigational product or planned involvement during the study period Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data, as assessed by the Investigator Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed) History of allergic disease or reactions likely to be exacerbated by any component of the vaccine Any history of anaphylaxis in reaction to vaccinations Pregnancy, lactation or 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 that may affect participation in the study Any other serious chronic illness requiring hospital specialist supervision Suspected or known current alcohol misuse as defined by an alcohol intake of greater than 25 standard UK units every week Suspected or known injecting drug use in the 5 years preceding enrolment Hepatitis B surface antigen (HBsAg) detected in serum Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless volunteer has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV ribonucleic acid (RNA) PCR at screening for this study) Volunteers unable to be closely followed for social, geographic or psychological reasons. Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. In the event of abnormal test results, confirmatory repeat tests will be requested. Procedures for identifying laboratory values meeting exclusion criteria are shown in SOP VC027 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 2 and 6: Body weight <50 kg or Body Mass Index (BMI) <18.0 at screening Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin) Use of anti-malarials within 30 days of CHMI Receipt of a COVID-19 vaccine within 2 weeks before the day of CHMI or planned receipt of a COVID-19 vaccine or prior to expected completion of antimalarial treatment (around 2 to 3 weeks after day of challenge based on experience in previous P. falciparum CHMI studies to date) An estimated ten-year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE). 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 Any other contraindications/known hypersensitivities to both Riamet and Malarone Any clinical condition known to prolong the QT interval History, or evidence at screening, of clinically significant arrhythmias, including clinically relevant bradycardia, prolonged QT interval or other clinically relevant ECG abnormalities Disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia Family history of congenital QT prolongation or sudden death Positive family history in both 1st AND 2nd degree relatives < 50 years old for cardiac disease History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait, G6PD deficiency or any haematological condition that could affect susceptibility to malaria infection