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Malaria affects around 515 million people each year, about a million of whom die from the disease. It is a major problem for those who live in affected areas as well as for travellers to affected areas. There is a great need for a safe, effective malaria vaccine. The purpose of this study is to test 2 new vaccination regimes that include a new malaria vaccine candidate, for their ability to prevent malaria infection.
The vaccines are different types of virus which contain genetic information (DNA) from the malaria parasite. This genetic material is named ME-TRAP. The aim is to use these viruses to help the body make an immune response against the malaria parasite. Both viruses are inactivated so that they are unable to multiply within the body.
The first vaccine virus is a weakened version of a common cold virus. Such adenoviruses occur in many strain types and commonly infect chimpanzees as well as people and this vaccine uses a strain originally derived from a chimpanzee. The vaccine is called AdCh63 ME-TRAP.
The other virus is Modified Vaccinia Ankara Virus, (MVA), which is a safer form of the vaccine virus previously widely used for smallpox vaccination. The vaccine is called MVA ME-TRAP.
This study will enable the investigators to assess:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Experimental | AdCh63 ME-TRAP prime followed by MVA ME-TRAP boost 8 weeks later and challenged by sporozoite 3 weeks after boost |
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| Group 2 | Experimental | AdCh63 ME-TRAP alone followed by sporozoite challenge 3 weeks later |
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| Group 3 | Experimental | Non-vaccinated Control for Groups 1 and 2 challenged with sporozoite |
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| Group 4 | Experimental | AdCh63 ME-TRAP prime followed by MVA ME-TRAP boost 8 weeks later and challenged by sporozoite 11 weeks after boost |
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| Group 5 | Experimental | AdCh63 ME-TRAP prime followed by MVA ME-TRAP boost 8 weeks later and challenged by sporozoite 3 weeks after boost |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AdCh63 ME-TRAP | Biological | 5 x 10*10 vp IM |
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| Measure | Description | Time Frame |
|---|---|---|
| Vaccine prevention (partial or complete) of malaria infection by sporozoite challenge | Approxiamately 5-16 months following last intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Safety of vaccine | Approxiamately 5-16 months following last intervention |
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Inclusion Criteria:
Exclusion Criteria:
Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period.
Prior receipt of an investigational malaria vaccine encoding ME-TRAP or any other investigational vaccine likely to impact on interpretation of the trial data
Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
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)
Pregnancy, lactation or intention to become pregnant during the study
Contraindication to both anti-malarial drugs (Riamet® and chloroquine)
o concomitant use with other drugs known to cause QT-interval prolongation, ( e.g. macrolides, quinolones, amiodarone etc)
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
Any history of anaphylaxis in reaction to vaccination
History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
History of serious psychiatric condition
Any other serious chronic illness requiring hospital specialist supervision
Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
Suspected or known injecting drug abuse
Seropositive for hepatitis B surface antigen (HBsAg)
Seropositive for hepatitis C virus (antibodies to HCV)
Seropositive for simian adenovirus 63 (antibodies to AdCh63) at a titre > 1: 200 ( EXCEPT CONTROL VOLUNTEERS)
Any other significant disease, disorder or finding, which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer's ability to participate in the study.
History of clinical P. falciparum malaria
Travel to a malaria endemic region during the study period or within the previous six months
Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis
Any other finding which in the opinion of the investigators would significantly increase the risk of having an adverse outcome from participating in the protocol or impair interpretation of the study data.
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| Name | Affiliation | Role |
|---|---|---|
| Adrian VS Hill, D.Phil, FRCP | University of Oxford | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford | Oxford | Headington | OX3 7LJ | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24284865 | Derived | Ewer KJ, O'Hara GA, Duncan CJ, Collins KA, Sheehy SH, Reyes-Sandoval A, Goodman AL, Edwards NJ, Elias SC, Halstead FD, Longley RJ, Rowland R, Poulton ID, Draper SJ, Blagborough AM, Berrie E, Moyle S, Williams N, Siani L, Folgori A, Colloca S, Sinden RE, Lawrie AM, Cortese R, Gilbert SC, Nicosia A, Hill AV. Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation. Nat Commun. 2013;4:2836. doi: 10.1038/ncomms3836. |
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| Group 6 | Experimental | Protected volunteers from Group 1 re-challenged with sporozoite after 6 months |
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| Group 7 | Experimental | Non vaccinated control for Groups 4-6, 8-10 challenged with sporozoite |
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| Group 8 | Experimental | 3 vaccinations of mixture formulation AdCh63 ME-TRAP and MVA ME-TRAP give at 8 weeks interval each followed by sporozoite challenge 3 weeks after last vaccination |
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| Group 9 | Experimental | 2 vaccinations of mixture formulation AdCh63 ME-TRAP and MVA ME-TRAP give at 8 weeks interval followed by sporozoite challenge 3 weeks after last vaccination |
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| Group 10 | Experimental | 3 vaccinations of mixture formulation AdCh63 ME-TRAP and MVA ME-TRAP give at 4 weeks interval each followed by sporozoite challenge 3 weeks after last vaccination |
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| MVA ME-TRAP | Biological | 2 x 10*8 pfu ID |
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| Sporozoite challenge | Other | Infected mosquito bite |
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| Mixture of AdCh63 ME-TRAP and MVA ME-TRAP intramuscularly | Biological | AdCh63 ME-TRAP 5 x 10*10 vp MVA ME-TRAP 2 x 10*8 pfu |
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| ID | Term |
|---|---|
| D008288 | Malaria |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
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