This is a single centre, randomized, placebo-controlled phase 1/2 study comparing two malaria vaccine candidates. The first vaccine candidate PfSPZ-CVac (Plasmodium falciparum sporozoites (PfSPZ) challenge administered with a chemoprophylactic antimalarial) will be chemoattenuated in vivo with the antimalarial Pyramax. The second vaccine candidate is prime- target vaccination with viral vectored vaccine candidate regime MVA ME-TRAP (Modified Vaccinia Ankara (MVA) multiple epitope thrombosponin-related adhesion protein (ME-TRAP)) and ChAd63 ME-TRAP (Chimpanzee adenovirus 63 (ChAd63). The safety and protective efficacy of both vaccine candidates will be to assessed by controlled human malaria infection with PfSPZ Challenge strain NF54 administered intravenously by syringe.

Inclusion Criteria:

• 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 if required.
• Residence in Tübingen or surroundings for the period of the trial.
• Women only: Must agree to practice continuous highly effective contraception for the duration of the study and until the end of relevant systemic exposure (a method which results in a low failure rate; i.e. less than 1% per year). Additionally, women will only be exposed to the PfSPZ-CVac/ME-TRAP products following a negative highly sensitive pregnancy test the day before immunization/CHMI.
• Agreement to refrain from blood donation during the course of the study and after the end of their involvement in the study according to the local and national blood banking eligibility criteria (which is a permanent refrain from blood donations after a malaria parasite infection).
• Provision of written informed consent to receive PfSPZ Challenge products or ME-TRAP products for immunization and subsequently for CHMI.
• Accept to be contacted (24/7) by mobile phone during the immunization and CHMI period.
• Willingness to take Pyramax during immunization (PfSPZ-CVac group) and a curative antimalarial regimen following CHMI.
• Agreement to stay overnight for observation during the period of intensive follow-up post-challenge if required.
• Answer all questions on the informed consent quiz correctly.
• A body mass index <35

Exclusion Criteria:

• History of P. falciparum malaria within the last 5 years.

• Prior receipt of malaria vaccine.

• Planned travel to malaria endemic areas during the study period.

• Use of drugs with known antimalarial activity within 30 days of study enrollment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin).

• Participation in other clinical trials or the intake of an investigational medicinal product within the last 90 days or planned receipt during the duration of this study

• Human Immunodeficiency Virus (HIV) infection.

• Any confirmed or suspected immunosuppressive or immunodeficient state (e.g. repeated and/or unusual infections), history of infection caused by opportunistic organisms any infection or combination of infections that suggest underlying immunodeficiency, history of meningitis, encephalitis, septic shock, life-threatening soft tissue infection, more than one pneumonia, asplenia and/or chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)).

• Use of immunoglobulins or blood products within 3 months prior to enrollment.

• Known (or signs consistent with) sickle cell anaemia, sickle cell trait, thalassemia or thalassemia trait, glucose-6-phosphate dehydrogenase deficiency.

• Pregnancy, lactation or intention to become pregnant during the study.

• Contraindications to the use of the following antimalarial medications: Atovaquone-proguanil, artemether-lumefantrine, artesunate, pyronaridine-artesunate, i.e.:

  • Known hypersensitivity to any of these drugs
  • intake of the following drugs: rifampicine, rifabutin, metoclopramide, warfarin, cumarine-derivatives, etoposide, antiretroviral drugs, imipramine, amytriptilin, clomipramin, carbamazepine, phenytoin, St. Johns wort, metoprolol, flecainide, propafenone, digoxin, dabigatran; drugs inducing QTc prolongation, drugs metabolized by CYP2D6, drugs inducing CAP3A4.

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (e.g. egg products, Kathon).

• History of clinically significant contact dermatitis.

• History of cancer within the last 5 years (except basal cell carcinoma of the skin and cervical carcinoma in situ).

• History of serious psychiatric condition that may affect participation in the study.

• Alcohol consumption should not exceed 24 g (men) or 12 g (women)/per day

• Haemoglobin <14 g/dl (men) or <12 g/dl (women)

• Suspected or known injected drug abuse in the 5 years preceding enrollment.

• Positive for hepatitis B surface antigen (HBs-antigen).

• Seropositivity for hepatitis C virus (antibodies to HCV)

• Clinical signs or symptoms of hepatic injury (such as nausea and/or abdominal pain associated with jaundice) or known liver disease (i.e. decompensated cirrhosis, Child-Pugh stage B or C).

• Renal abnormalities

• GFR <30ml/min (glomerular filtration rate)

• Presence or past history of cardiac arrhythmia or an abnormal electrocardiogram or suspected coronary heart disease or family history for sudden cardiac death.

• Known or suspected porphyria.

• Volunteers unable to be closely followed for social, geographic or psychological reasons.

• History of seizure (except uncomplicated febrile convulsion at childhood)

• Immunization with more than 3 other vaccines within four weeks.

• Electrolyte disturbance.