This is an open label, multi-centre phase I/IIa sporozoite-challenge trial to assess the safety, immunogenicity and efficacy of two combination ChAd63-MVA heterologous prime-boost vaccination regimens. All volunteers recruited will be healthy, malaria naïve adults aged between 18 and 45 years. To determine the efficacy of each of two combinations of heterologous prime-boost immunisation strategies: 1. ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS 2. ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS and ChAd63-MVA AMA1 The study will be conducted at the University of Oxford's Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford, UK and the Wellcome Trust Clinical Research Facility in Southampton, UK. The malaria challenge will take place at the insectary at Imperial College (Infection and Immunity Section) in London, UK.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
48
Mixture of ChAd63 CS 5 x 1010 vp and ChAd63 ME-TRAP 5 x 1010 vp. Intramuscular needle injection.
Mixture of MVA CS 2 x 108 pfu and MVA ME-TRAP 2 x 108 pfu. Intramuscular needle injection.
Mixture of ChAd63 CS 5 x 1010 vp, ChAd63 ME-TRAP 5 x 1010 vp, and ChAd63 AMA1 5 x 1010 vp. Intramuscular needle injection.
Mixture of MVA CS 1.33 x 108 pfu, MVA ME-TRAP 1.33 x 108 pfu, and MVA AMA1 1.33 x 108 pfu. Intramuscular needle injection.
Approximately three weeks post MVA dosing.
Wellcome Trust CRF, Southampton General Hospital
Southampton, Hampshire, United Kingdom
Centre for Clinical Vaccinology and Tropical Medicine
Oxford, Oxfordshire, United Kingdom
Infection and Immunity Section, Imperial College of Science, Technology and Medicine
London, United Kingdom
The effectiveness of ChAd63-MVA ME-TRAP combined with ChAd63-CS and ChAd63-MVA AMA1 at preventing malaria infection.
To assess the efficacy of each of two combinations of heterologous prime-boost immunisation strategies: 1. ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS 2. ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS and ChAd63-MVA AMA1 Kaplan-Meier analysis of time to blood stage infection in vaccinees compared to unvaccinated control volunteers. Comparison of the number of individuals who develop malaria infection between vaccinees and unvaccinated control volunteers.
Time frame: Up to 30 days post challenge
Safety and immunogenicity of ChAd63-MVA ME-TRAP, ChAd63-MVA CS, ChAd63-MVA AMA1.
To assess the safety and immunogenicity of heterologous prime-boost immunisation of malaria-naïve individuals with ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS or with ChAd63-MVA CS plus ChAd63-MVA AMA1. The safety of the vaccine regimens will be assessed by analysing actively and passively collected data from clinical review of volunteers and laboratory measurements. The ability of the vaccines to induce malaria-specific immune responses immunogenicity) will be assessed by the following laboratory tests; (A) Interferon gamma ELISPOT. (B) Flow cytometry to measure T cell responses. Other laboratory investigations including microarray analysis may be performed.
Time frame: Up to 7 months post first vaccination
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