Safety and Protective Efficacy of IV Immunization With Cryopreserved PfSPZ Under A/P Chemoprophylaxis

This is an interventional prevention trial for Malaria Read More

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 if required.
• Residence in Tübingen or surroundings for the period of the trial.
• Women only: Must agree to practice continuous effective contraception for the duration of the study (a method which results in a low failure rate; i.e. less than 1% per year).
• 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 (currently four years in Germany).
• Provision of written informed consent to receive PfSPZ Challenge for immunization and subsequently for CHMI.
• Reachable (24/7) by mobile phone during the immunization and CHMI period.
• Willingness to take A/P during immunization 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 18-35.

Exclusion Criteria:

• History of P.falciparum malaria.
• Planned travel to malaria endemic areas during the study period.
• Use of systemic antibiotics with known antimalarial activity within 30 days of study enrollment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin,erythromycin, fluoroquinolones, or azithromycin).
• Receipt of an investigational product in the 90 days preceding enrollment, or planned receipt during the study period.
• 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 enrolment.
• Known (or signs consistent with) sickle cell anemia, 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: A/P, artemether-lumefantrine
• 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 60 g (men) or 40 g (women) per day or a carbohydrate deficient transferrin (CDT) level ≥2.5%.
• Suspected or known injected drug abuse in the 5 years preceding enrollment.
• Positive for hepatitis B surface antigen (HBs-antigen).
• Seropositive for hepatitis C virus (antibodies to HCV).
• Falling in moderate risk or higher categories for fatal or non-fatal cardiovascular event within 5 years (>10%) determined by non-invasive criteria for cardiac risk 84.
• Abnormal electrocardiogram on screening: pathologic Q wave and significant ST-T wave changes, left ventricular hypertrophy, clinically significant arrythmias, left bundle branch block, secondary or tertiary AV block
• A QT/QTcB interval >450 ms.
• Volunteers unable to be closely followed for social, geographic or psychological reasons.
• CrCL <30ml/min
• History of seizure (except uncomplicated febrile convulsion at childhood)
• Immunization with more than 3 other vaccines within the past month
• Any other significant disease, disorder, finding at medical history, biochemistry, hematology tests, urine analysis results or at clinical examination which, in the opinion of the investigator, 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.