Malaria
Conditions
Interventions
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Only participants who meet all the inclusion criteria will be enrolled into the trial; • Groups 1, 2 and 6-9: Healthy male or female infants aged 5-17 months at the time of enrolment with signed consent obtained from parents or guardians. • Groups 3-5: Healthy male or female adults aged 18-45 years at the time of enrolment with signed consent. • Groups 3-5 (Female participants only): Must be non-pregnant (as demonstrated by a negative urine pregnancy test), and practice continuous effective contraception for the 24 to 30 month duration of the study (see section 9.9). • Planned long-term (at least 24 months from the date of recruitment) or permanent residence in the study area. • Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or infants with Z-score of weight-for-age within ±2SD.
Exclusion criteria
Exclusion criteria: The participant may not enter the trial if ANY of the following apply: • Clinically significant congenital abnormalities as judged by the PI or other delegated individual • Clinically significant history of skin disorder (psoriasis, contact dermatitis etc.), allergy, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease and neurological illness as judged by the PI or other delegated individual. • 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). • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). • History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g., Kathon, neomycin, betapropiolactone. • Any history of anaphylaxis in relation to vaccination. • Clinically significant laboratory abnormality at grade 2 or above as judged by the PI or other delegated individual. • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. • Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days following each study vaccination. This excludes COVID-19 vaccines, which should not be received between 14 days before to 7 days after any study vaccination, and EPI vaccines (for infants), which should not be received between 14 days before to 28 days after any study vaccination. • History of vaccination with previous malaria vaccines. Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment in adults or at any time for infants, or planned use during the study period. • Suspected or known current alcohol abuse. Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment in adults or at any time for infants, or planned use during the study period. • Suspected or known current alcohol abuse. • Suspected or known injecting drug abuse in the 5 years preceding enrolment. • Seropositive for hepatitis B surface antigen (HBsAg), hepatitis C (HCV IgG) or HIV. For infants, any history of vertical exposure to HIV infection. • Any other finding which in the opinion of the PI or other delegated individual would increase the risk of an adverse outcome from participation in the trial. • Positive malaria by PCR screening. • Female participant who is pregnant, lactating or planning pregnancy during the course of the trial. • Scheduled elective surgery or other procedures requiring general anaesthesia during the trial. • Any other significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. The following parameters will be assessed: • Occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination • Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following each vaccination • Occurrence of unsolicited adverse events for 28 days following the vaccination • Change from baseline for safety laboratory measures for 28 days following vaccination • Occurrence of serious adverse events during the whole study duration Solicited AE data will be collected daily for the first seven days following first vaccination and three days following each subsequent vaccination via clinic and home visits. Unsolicited AE data will be collected at each visit via clinical review, clinical examination (including observations) and laboratory results. This AE data will be tabulated, detailing frequency, duration and severity of AEs. Haematological and biochemical laboratory values will be presented according to local grading scales. Serious adverse events (SAEs), adverse events (AEs) of special interest and withdrawal due to AE(s)/SAE(s) will be described in detail. Volunteers will be followed for approximately 24-30 months following initial trial vaccination and approximately 22-24 months following the third dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| Priority immunology: • RH5 serology (participants vaccinated with RH5.2-VLP only) • R21 serology (participants vaccinated with R21 only) • Hepatitis B serology • Growth Inhibition Activity (GIA) (participants vaccinated with RH5.2-VLP only) • Serum total IgG concentration determination • Inhibition of sporozoite invasion assay (ISI) (participants vaccinated with R21 only) Possibilities for exploratory immunology (to be confirmed): • P. falciparum anti-schizont ELISA • Flow cytometry (B cell/TfH/ICS) (adults only) • Peptide arrays • mAb isolation (adults only) The above will be detailed further in the Immunology Analysis Plan. Blood samples will be taken at the timepoints shown in table 4. Samples are required from a number of key timepoints including baseline and post vaccination of V+7 (adults only), V+14, V+28 to allow for antibody kinetics and magnitude assessment, and late timepoints to assess longevity of response. For the priority immunology, ELISA will be performed at every timepoint where ‘immunology serum’ is shown in table 4. GIA will be performed at peak of response after the third vaccination, based on previous work this is likely to be at V3+14 or V3+28. A minimum of 2mL serum is required to perform GIA on individuals to assess functionality of antibodies, so the bleeds at V3+14 (i.e. day 70/196) therefore need to be at least 4mL due to ~50% being serum. Taking less than 4mL of serum at these key time-points would compromise our ability to meet our key immunology endpoints and therefore we require serum collection at V+28 in case V+14 sample is compromised to ensure antibody functionality in GIA can be assessed. | — |
Countries
Gambia
Contacts
Public ContactAngela M Minassian
Chief Investigator
Outcome results
None listed