Malaria is a major public health problem. There were around 240 million cases of malaria and 627,000 deaths worldwide in 2020. Most of the deaths are in children under five living in Africa. It is a major problem for those who live in affected areas and for travellers. There is a great need for a safe, effective malaria vaccine. This study is being done to evaluate an experimental malaria vaccine for its safety and also look at the body's immune response to the vaccine. The vaccine tested in this study is called and "RH5.1". This is given with an adjuvant called "Matrix-M". This is a substance to improve the body's response to a vaccination. The aim is to use the vaccines and adjuvant to help the body make an immune response against parts of the malaria parasite. This study will assess: 1. The safety of the vaccines in healthy participants. 2. The response of the human immune system to the vaccines. This will be achieved by giving participants three doses of the RH5.1 vaccines at two different dose levels (10 micrograms and 50 micrograms). One group will have 3 doses of 10 micrograms given at 0, 1 and 6 months whilst the other will receive 2 doses of 50 micrograms (at 1 and 2 months) followed by a 10 microgram dose at 6 months- known as a 'delayed fractional dose'. Blood tests and information about any symptoms will be performed/collected that occur after vaccination. Information from previous studies suggests that a delayed fractional dose improves the immune response to the vaccine, particularly in terms of the antibody response. Current prediction is that this improvement is due to the delay in dosing, rather than the reduction in dose, and this study will help to answer that. Having a vaccine at a single dose is important for efficient production and dosing for vaccines rolled out in national programs so being able to move away from 'delayed fractional dose' regimens to 'delayed final dose' regimens will be important for vaccine development.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
50 µg of Matrix-M adjuvant with RH5.1 at different doses on days 0 and 28.
Sheffield Teaching Hospitals, Royal Hallamshire Hospital
Sheffield, United Kingdom
To assess the safety of RH5.1 soluble protein in Matrix-M in healthy adult volunteers by assessing the occurrence of solicited reactogenicity following each vaccinations
Occurrence of solicited local/systemic reactogenicity signs and symptoms for 7 days. following each vaccination. These will be tabulated, detailing frequency, duration and severity of signs and symptoms.
Time frame: 7 days following each vaccination
To assess the safety of RH5.1 soluble protein in Matrix-M in healthy adult volunteers by assessing the occurrence of unsolicited adverse events following each vaccinations
Occurrence of unsolicited adverse events for 28 days following the vaccination. These will be tabulated, detailing frequency, duration and severity of AEs.
Time frame: 28 days following each vaccination
To assess the safety of RH5.1 soluble protein in Matrix-M in healthy adult volunteers by comparing safety laboratory measures following each vaccinations
Change from baseline for safety laboratory measures for 28 days following vaccination. Haematological and biochemical laboratory values will be presented according to local grading scales.
Time frame: 28 days following each vaccination
To assess the safety of RH5.1 soluble protein in Matrix-M in healthy adult volunteers by assessing the occurrence of serious adverse events
Occurrence of serious adverse events during the whole study duration. These will be tabulated, detailing frequency, duration and severity of SAEs.
Time frame: During Whole study duration (547 days)
To assess the humoral immunogenicity of RH5.1 soluble protein with Matrix-M when administered to healthy volunteers at different doses.
Serum ELISA response, quantitative antigen-specific IgG antibody levels (µg/mL readout) over time - analysis of peak responses and longevity, with comparison before and after vaccination
Time frame: From a number of key timepoints (Baseline up to day 547)
To compare the anti-RH5 serum IgG functional immunogenicity between the two groups receiving soluble RH5.1 at different doses by assessing purified IgG versus GIA titration (quality analysis)
Immunogenicity will be assessed to characterise quantity, quality and longevity of serum anti-RH5 IgG responses as measured by standardised ELISA. The growth inhibition activity will be used to determine functionality of these responses and allow quality analysis. Comparisons between two groups receiving soluble RH5.1 protein at different doses will be made post vaccination to determine how differing doses affect these responses.
Time frame: After each vaccinations (D0, D28 and D182)
To compare differences in the innate immune responses following the first and third vaccinations and correlated these with adverse event data and adaptive immune responses
Innate immune cell analyses will include flow cytometry analyses and quantitative measurements of pro-inflammatory cytokines to phenotype innate immune cell populations primarily in the first 7 days following vaccination.
Time frame: 7, 28 days following first and third vaccinations
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