A study to compare two dosing regimens for a new malaria vaccine

INTERVENTION: Participants are randomised through the REDCap database. Group 1: 10 µg of RH5.1 with 50 µg of Matrix‐M given on Day 0, Day 28 and Day 182, Intramuscular injection in the deltoid region of the non‐dominant arm. Follow up until Day 547 (with visit window applied). Group 2: 50 µg of RH5.1 with 50 µg of Matrix‐M at Day 0 and Day 28 and reduced dosage 10 µg of RH5.1 with 50 µg of Matrix‐M at Day 182. The route of administration and follow‐up activity is the same as Group 1. CONDITION: Malaria (African strain) ; Infections and Infestations PRIMARY OUTCOME: 1. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination Listed signs and symptoms (Pain, Itching, warmth, Feverish, Muscle Aches, Joint Aches, Headache, Fatigue, Nausea, Generally Unwell) measured using a 0‐3 grading scale on Day 0 to Day 6 following each vaccination.; 2. Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following each vaccination Listed signs and symptoms (Pain, Itching, warmth, Feverish, Muscle Aches, Joint Aches, Headache, Fatigue, Nausea, Generally Unwell) measured using a 0‐3 grading scale on Day 0 to Day 6 following each vaccination.; 3. Occurrence of unsolicited adverse events for 28 days following the vaccination Participant listed signs and symptoms measured using a 0‐3 grading scale from Day 0 to Day 28 following each vaccination.; 4. Change from baseline for safety laboratory measures for 28 days following vaccination Listed laboratory measures measured using appropriate laboratory parameters on Day 0 to Day 28 following each vaccination.; 5. Occurrence of serious adverse events during the whole study duration SAEs measured using a 0‐3 grading system during the whole study duration. ; SECONDARY OUTCOME: 1. Serum ELISA response: ; 1.1. Quantitative antigen‐specific IgG antibody levels (µg/mL readout) over time – analysis of peak responses and longevity anti‐RH5 specific total IgG quantity assessed by standardised ELISA at every vaccination and follow‐up visits. ; 1.2. Antigen‐specific antibody subclass/isotype analysis anti‐RH5 specific total IgG1, IgG2, IgG3, IgG4, IgA and IgM responses assessed by standardised isotype/subclass ELISA at baseline, peak and late timepoints; 1.3. Antigen‐specific antibody avidity analysis anti‐RH5 specific total IgG avidity responses assessed by chaotropic displacement ELISA at baseline, peak and late timepoints; 2. In vitro GIA against 3D7 clone P. falciparum parasites using purified total IgG and a single‐cycle pLDH readout assay anti‐RH5 specific purified IgG growth inhibition activity as determined by growth inhibition assay at baseline and peak responses.; 3. Purified IgG ELISA versus GIA titration “Quality Analysis” Quality (concentration of RH5 specific total IgG required to give 50% growth inhibition) analysis – GIA titre determined as per 2. Purified IgG tested on 1. And plotted against each other to give EC50%.; 4. Total IgG serum concentration determination Serum total IgG concentration determined by HPLC at GIA timepoints (baseline and peak response) to allow normalisation of actual physiological responses.; INCLUSION CRITERIA: 1. Healthy adult aged 18 to 50 years 2. Able and willing (in the Investigator’s opinion) to comply with all study requirements 3. Willing to allow the Investigators to discuss the volunteer’s medical history with their GP 4. Participants of childbearing potential only: must practice continuous effective contraception for the duration of the study (see section 9.9) 5. Agreement to refrain from blood donation for the duration of the study 6. Able and willing to provide written informed consent to participate in the trial