Malaria (African strain) Infections and Infestations
Conditions
Interventions
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-dom
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
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
Exclusion criteria
Exclusion criteria: 1. History of clinical malaria (any species) or previous participation in any malaria (vaccine) trial or controlled human malaria infection (CHMI) study 2. Travel to a clearly malaria endemic locality during the study period or within the preceding 6 months 3. Use of immunoglobulins or blood products (e.g. blood transfusion) in the last 3 months 4. Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days following each study vaccination, with the exception of COVID-19 vaccines, which should not be received between 14 days before to 7 days after any study vaccination 5. Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period 6. Concurrent involvement in another clinical trial involving an investigational product or planned involvement during the study period 7. Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data, as assessed by the Investigator 8. 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) 9. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine 10. Any history of anaphylaxis 11. Pregnancy, lactation or intention to become pregnant during the study 12. Body mass index of 35 13. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ) 14. History of serious psychiatric condition that may affect participation in the study 15. Any other serious chronic illness requiring hospital specialist supervision 16. Suspected or known current alcohol misuse as defined by an alcohol intake of greater than 25 standard UK units every week 17. Suspected or known injecting drug use in the 5 years preceding enrolment 18. Hepatitis B surface antigen (HBsAg) detected in serum 19. Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless volunteer has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV ribonucleic acid (RNA) PCR at screening for this study) 20. Volunteers unable to be closely followed for social, geographic or psychological reasons. 21. Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. In the event of abnormal test results, confirmatory repeat tests will be requested. Procedures for identifying laboratory values meeting exclusion criteria are shown in SOP VC027 22. Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data 23. Inability of the study team to contact the volunteer’s GP to confirm medical history and safety to participate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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. | — |
Countries
England, United Kingdom
Contacts
Public ContactRachel;Ruth Cowan;Payne
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Outcome results
None listed