VAC069: A Study of Blood-stage Controlled Human P. Vivax Infection

Inclusion Criteria: * Healthy adult aged 18 to 50 years. * Red blood cells positive for the Duffy antigen/chemokine receptor (DARC). * Normal serum levels of Glucose-6-phosphate dehydrogenase (G6PDH). * Negative haemoglobinopathy screen * 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. * Women only: Must practice continuous effective contraception for the duration of the clinic visits (first 3 months post-CHMI). * Agreement to permanently refrain from blood donation * Written informed consent to participate in the trial. * Reachable (24/7) by mobile phone during the period between CHMI and completion of all antimalarial treatment. * Willing to take a curative anti-malarial regimen following CHMI. * Willing to reside in Oxford for the duration of the study, until antimalarials have been completed. * Answer all questions on the informed consent quiz correctly. Exclusion Criteria: * History of clinical malaria (any species). * Travel to a clearly malaria endemic locality during the study period or within the preceding six months. * Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g.trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin). * Haemoglobin \<120 g/L for a female volunteer or \<130 g/L for a male volunteer prior to primary CHMI. (However, for enrolment into secondary and tertiary CHMIs slightly lower haemoglobin values (≤0.5 g/L) will be permitted at the discretion of the Investigator, to account for the blood volume donated during the previous CHMI). * Receipt of immunoglobulins within the three months prior to enrolment. * Receipt of blood transfusion at any time in the past. * Peripheral venous access unlikely to allow twice daily blood testing (as determined by the Investigator). * Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period. * Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data or the P. vivax parasite as assessed by the Investigator. * Planned receipt of a COVID-19 vaccine between 2 weeks before the day of CHMI until completion of antimalarial treatment * 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 malaria infection. * Pregnancy, lactation or intention to become pregnant during the study. * 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 clinical condition known to prolong the QT interval. * History of cardiac arrhythmia, including clinically relevant bradycardia. * Disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia. * Family history of congenital QT prolongation or sudden death. * Contraindications to the use of both of the proposed anti-malarial medications Riamet and Malarone. * 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 abuse as defined by an alcohol intake of greater than 25 standard UK units every week. * Suspected or known injecting drug abuse in the 5 years preceding enrolment. * Hepatitis B surface antigen (HBsAg) detected in serum. * Seropositive for hepatitis C virus (antibodies to HCV) at screening or at C-7 (unless has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV RNA PCR at screening for this study). * Positive family history in both 1st AND 2nd degree relatives \< 50 years old for cardiac disease. * 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. * 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 6-13: Body weight \<50Kg, as measured at screening Exclusion criteria on day of CHMI: * Acute disease, defined as moderate or severe illness with or without fever. * Current COVID-19 infection, defined as ongoing symptoms with positive COVID-19 PCR swab test taken during current illness or positive COVID-19 PCR swab test within preceding 14 days without symptoms. * Pregnancy. * Potential volunteers who are due to have a COVID-19 vaccine in the period between 2 weeks before the day of malaria challenge and expected time of completion of malaria treatment will not be enrolled (estimate up to 3 weeks after day of challenge based on experience in this study to date). If a volunteer receives an appointment for COVID-19 vaccination after they have undergone malaria challenge but before reaching malaria diagnosis criteria, they will be advised to delay their COVID-19 vaccination until after reaching malaria diagnostic criteria and completion of antimalarial treatment. If a participant does not wish to delay their COVID-19 vaccination, they will be treated with antimalarial treatment at that time point and withdrawn from the study but will be encouraged to complete follow-up for safety.