Healthy volunteers, testing investigational Malaria vaccines Infections and Infestations
Conditions
Interventions
Current interventions as of 01/04/2026:
We will testing the safety and efficacy of the vaccines, R78C and RH5.1, which are given in combination with the adjuvant Matrix-M. Group 1 participants will
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 10/09/2025: 1. Healthy adult aged 18 to 45 years. 2. Able and willing (in the Investigator’s opinion) to comply with all study requirements. 3. Willing to allow the Investigators to access participant’s electronic medical records and discuss the participant’s medical history with their GP. 4. Able and willing to provide written informed consent to participate in the trial. 5. Participants of childbearing potential only: must practice continuous effective contraception for the duration of the study. 6. Negative haemoglobinopathy screen (including screening for sickle cell disease and alpha and beta thalassaemia) and normal G6PD levels. 7. Agreement to permanently refrain from blood donation, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines. 8. Reachable (24 hours a day) by mobile phone during the period between CHMI and completion of antimalarial treatment. 9. Willing to take a curative anti-malaria regimen following CHMI. 10. Able to answer all questions on the informed consent questionnaire correctly at first or second attempt. 11. Willing to be registered on the TOPS database (The Over volunteering Prevention System; www.tops.org.uk). _____ Previous inclusion criteria: 1. Healthy adult aged 18 to 45 years. 2. Able and willing (in the Investigator’s opinion) to comply with all study requirements. 3. Willing to allow the Investigators to access participant’s electronic medical records and discuss the participant’s medical history with their GP. 4. Able and willing to provide written informed consent to participate in the trial. 5. Participants of childbearing potential only: must practice continuous effective contraception for the duration of the study. 6. Negative haemoglobinopathy screen (including screening for sickle cell disease and alpha and beta thalassaemia) and normal G6PD levels. 7. Agreement to permanently refrain from blood donation, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines. 8. Reachable (24 hours a day) by mobile phone during the period between CHMI and completion of antimalarial treatment. 9. Willing to take a curative anti-malaria regimen following CHMI. 10. Able to answer all questions on the informed consent questionnaire correctly at first or second attempt. 11. Willing to be registered on the TOPS database (The Over volunteering Prevention System; www.tops.org.uk). Group 2 only: 12. Participant in Group 1, 2 or 4 of the VAC089 trial.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 10/09/2025: 1. History of clinical malaria (any species) or previous participation in any malaria vaccine trial 2. Planned travel to a clearly malaria-endemic locality during the study period or previous travel to a malaria endemic locality within the preceding six months. 3. Use of immunoglobulins or blood products (e.g. blood transfusion) in the last three 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 and flu vaccines, which should not be received between 14 days before to 7 days after any study vaccination. 5. Receipt of a vaccine within 2 weeks before the day of CHMI or planned receipt of a vaccine prior to expected completion of antimalarial treatment (around 2 to 3 weeks after day of challenge based on experience in previous P. falciparum CHMI studies to date). 6. Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period. 7. Concurrent involvement in another clinical trial involving an investigational product or planned involvement during the study period. 8. Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data, as assessed by the Investigator. 9. 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). 10. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. 11. Any history of anaphylaxis. 12. Pregnancy, lactation or intention to become pregnant during the study. 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. 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 participant 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. Body weight <50 kg or Body Mass Index (BMI) <18.0 kg/m² at screening. 21. Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin). 22. Use of anti-malarials within 30 days of CHMI. 23. An estimated ten-year risk of fatal cardiovascular disease of =5% at screening, as determined by the Systematic Coronary Risk Evaluation 2 (SCORE2). 24. Use of medications known to cause prolongation of the QT interval and existing contraindication to the use of Malarone. 25. Use of medications known to have a potentially clinically significant interaction with Riamet and Malarone. 26. Any other contraindications/known hypersensitivities to both Riamet and Malarone. 27. Any clinical condition known to prolong the QT interval. 28. History, or evidence at screening, of clinically
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 10/09/2025: 1. Solicited local and systemic adverse events measured after vaccination until day 7 post vaccination. 2. Unsolicited adverse events measured after each vaccination until day 28 post vaccination. 3. Change from baseline measured for safety laboratory measures for 28 days following vaccination 4. Medically attended adverse events collected during the entire study period 5. Serious adverse events (which includes AESIs) collected during the entire study period. 6. Comparison of time to diagnosis measured between Groups 1 and 2 _____ Previous primary outcome measure: 1.Solicited local and systemic adverse events measured after vaccination until day 7 post vaccination. 2.Unsolicited adverse events measured after each vaccination until day 28 post vaccination. 3.Change from baseline measured for safety laboratory measures for 28 days following vaccination 4.Medically attended adverse events collected during the entire study period 5.Serious adverse events (which includes AESIs) collected during the entire study period. 6.Comparison of time to diagnosis measured between Groups 1, 2 and 3 (Groups 2a and 2b will be pooled) | — |
Secondary
| Measure | Time frame |
|---|---|
| Current key secondary outcome(s) as of 01/04/2026: 1. Quantitative antigen-specific IgG antibody levels (µg/mL readout) measured over time – analysis of peak responses and longevity 2. In vitro GIA against 3D7 clone P. falciparum parasites measured using purified total IgG and a single-cycle pLDH readout assay _____ Previous secondary outcome measures as of 10/09/2025: 1. Quantitative antigen-specific IgG antibody levels (µg/mL readout) measured over time – analysis of peak responses and longevity 2. In vitro GIA against 3D7 clone P. falciparum parasites measured using purified total IgG and a single-cycle pLDH readout assay 3. Purified IgG ELISA versus GIA titration “Quality Analysis” 4. Frequency of vaccine-specific B cells in axillary lymph nodes as measured by flow cytometry _____ Previous secondary outcome measures: 1. Quantitative antigen-specific IgG antibody levels (µg/mL readout) measured over time – analysis of peak responses and longevity 2. In vitro GIA against 3D7 clone P. falciparum parasites measured using purified total IgG and a single-cycle pLDH readout assay | — |
Countries
United Kingdom
Contacts
Public ContactAngela Minassian
Outcome results
None listed