The purpose of this study is to assess two types of new malaria vaccines in different combinations. The study will enable us to assess: 1. The ability of the vaccines to prevent malaria infection. 2. The safety of the vaccines in healthy participants. 3. The response of the human immune system to the vaccines. We will do this by giving 48 participants three sets of vaccinations over 8 weeks, then exposing them to malaria infection by allowing mosquitoes infected with malaria to bite under carefully regulated conditions. We will follow participants closely to observe if and when they develop malaria. If the vaccine combination provides some protection against malaria, participants will take longer to develop malaria than usual or will not develop malaria at all. We will also recruit 4 individuals to be control subjects - these participants won't receive any vaccinations but will be challenged with malaria. Vaccinated volunteers who do not develop malaria infection in the blood after being infected with malaria by mosquito bite the first time may be invited back to be again infected with malaria in a repeat challenge experiment. This would happen approximately 5-7 months after the first challenge. The purpose of this second challenge will be to see how long the protection of the investigational vaccine against malaria lasts.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
48
NIHR WTCRF, University Hospital Southampton NHS Foundation Trust
Southampton, Hampshire, United Kingdom
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford
Oxford, Oxfordshire, United Kingdom
Surrey Clinical Research Centre, University of Surrey
Guildford, Surrey, United Kingdom
NIHR/Wellcome Trust Imperial CRF, Hammersmith Hospital, Imperial College NHS Trust
London, United Kingdom
Efficacy of a combination immunization regimen with ChAd63/MVA ME-TRAP given concomitantly with RTS,S/AS01B against malaria sporozoite challenge.
Use statistical analysis to compare number of completely protected individuals (those who do not, by Day 23 following sporozoite challenge, develop blood stage infection measured by occurrence of P. falciparum parasitemia, assessed by blood slide)
Time frame: 6 months
Safety of a combination immunization regimen with ChAd63/MVA ME-TRAP given concomitantly with RTS,S/AS01B against malaria sporozoite challenge.
Occurrence of solicited and unsolicited adverse events will be monitored. Solicited and unsolicited AE data will be collected at each clinic visit. It will be collected from diary cards, clinical review, clinical examination (including observations) and laboratory results. This AE data will be tabulated and frequency, duration and severity of AEs compared between groups.
Time frame: 6 months
Immunogenicity generated in malaria naïve individuals of two different dosing regimens of RTS,S/AS01B given concomitantly with ChAd63/MVA ME-TRAP, and of RTS,S/AS01B alone at either full standard dose or with a reduced third dose.
To document immunogenicity measures, capturing humoral and cellular immune responses to both ChAd63/MVA ME-TRAP and RTS,S as follows: Anti-CS (RT, C-term, full-length), anti-HBs, and anti-ME-TRAP antibody titers; frequency of CS-specific, HBs-specific, and TRAP and ME specific T cells; ChAd63 neutralizing antibody titers; avidity index of anti-CS antibodies. To undertake exploratory analysis of the correlation of these measures with vaccine efficacy. To, furthermore, undertake an exploratory analysis of transcriptomic correlates of vaccine immunogenicity and efficacy. This may be undertaken by microarray analysis or RNA sequencing or both techniques.
Time frame: 6 months
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