Assessment of protection against malaria by sporozoite challenge of healthy adults vaccinated with AdCh63 ME-TRAP and MVA ME-TRAP

INTERVENTION: Product Name: Chimapnzee adenovirus expressing ME‐TRAP Product Code: AdCh63 ME‐TRAP Pharmaceutical Form: Solution for injection Product Name: Modified Vaccinia Ankara expressing ME‐TRAP Product Code: MVA ME‐TRAP Pharmaceutical Form: Solution for injection CONDITION: Malaria PRIMARY OUTCOME: Main Objective: To assess if volunteers who received AdCh63 ME‐TRAP alone, as a homologous prime and boost, or as a heterologous boost with MVA ME‐TRAP are protected wholly or partially against malaria infection in a sporozoite challenge model. This will be determined by noting the number of subjects who develop malaria infection and the time in hours between exposure and parasitaemia as detected by thick‐film blood smear or clinical symptoms in the presence of positive PCR, and compared with controls Primary end point(s): Primary Evaluation Criteria; Definition of the Criteria; The protection against malaria infection in a sporozoite challenge model will be assessed by measuring the number of subjects who develop malaria infection and the time (in hours) between exposure and parasitaemia as detected by thick‐film blood smear, and compared with controls.; End‐points: ; Primary: One thick smear positive for one or more morphologically‐normal parasites during the 21 day observation period, OR; Secondary: Subject is manifesting typical clinical symptoms or signs of malaria in the opinion of the Chief Investigator (such as fever >37.5?C, rigors, moderate or severe myalgia, in the absence of another obvious cause) and has negative blood smears but has a PCR result that is positive for malaria.; Parameters to be Measured; Clinical Symptoms; Definitions:; ; No solicited adverse events will be recorded, but the following predictable symptoms of malaria will be enquired about at each visit :; • Symptoms of feverishness; • Chills; • Rigors; • Sweats; • Headache; • Anorexia; • Nausea / vomiting; • Diarrhoea; • Myalgia /Arthralgia; • Low back pain; Subjects will be instructed to record their oral temperature with the thermometer provided should they feel feverish.; The subjects will be instructed to contact the investigator immediately should they manifest any signs or symptoms they perceive as serious.; ; ; ; ; ; Assessment of Severity; Intensity of the general adverse events will be assessed as described: ; GRADE 0 None; GRADE 1 Mild: Transient or mild discomfort (< 48 hours); no medical intervention/therapy required; GRADE 2 Moderate: Mild to moderate limitation in activity ‐ some assistance may be needed; no or minimal medical intervention/therapy required; GRADE 3 Severe: Marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalisation possible; GRADE 4 Serious, life‐threatening: Extreme limitation in activity, significant assistance required; significant medical intervention/therapy required, hospitalisation or hospice care probable (see also 5.4.1.); ; Assessment of Outcome; Outcome will be assessed as:; 1 = Recovered; 2 = Recovered with sequelae; 3 = Died; 4 = Unknown; 5 = Ongoing at subject study conclusion (active phase) ; ; Parasitological Parameters; The parasitaemia will be assessed by thick smears and PCR.; Method and Timing of Measurement; Clinical signs: ; The clinical assessment and the check of vital signs will be performed and recorded at each timepoint from visit 4 to visit 29. ; Parasitology parameters: ; Blood smears and PCR will be performed for each volunteer, from visit 1 to visit 27. From D6 to D14, the samples will be taken twice a day (approximately 12 hourly).; After a positive blood film, blood samples will be collected daily until two consecutive negative thick smears are obtained. These will be examined by blood smear examination immediately. PCR analysis will also be done until the first positive thick smear.; .; Secondary Evaluation Criteria; Immunological assays will be conducted according to the procedures established in the test laboratories. With the volunteers’ informed consent, any leftover cells and serum will be frozen for future immunological analysis of malaria‐specific responses.; Tertiary Evaluation Criteria; Durability of immunity in protected individuals will be measured by a re‐challenge and reassessing primary and secondary criteria as described above.; Secondary Objective: To measure the safety of the vaccination regimes and to measure ex‐vivo and cultured IFN‐? ELISPOT responses to the ME‐TRAP antigens and anti‐sporozoite antibodies before and after malaria infection. If there is evidence of partial or complete protection by the vaccinations then we will explore immunological correlates of protective immunity.; To assess long term efficacy of AdCh63 ME‐TRAP and MVA ME‐TRAP in a re‐challenge of volunteers protected at initial malaria challenge. INCLUSION CRITERIA: Inclusion Criteria The volunteer must satisfy all the following criteria to be eligible for the study: • Healthy adult aged 18 to 50 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 • For females only: willingness to practise effective contraception throughout the study • Agreement to refrain from blood donation during the course of the study • Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range