A Study to Assess the Experimental Malaria Vaccines RH5.2-VLP and R21

Inclusion Criteria:

• Groups 1, 2 and 6-9: Healthy male or female infants aged 5-17 months at the time ofenrolment with signed consent obtained from parents or guardians.

• Groups 3-5: Healthy male or female adults aged 18-45 years at the time of enrolmentwith signed consent.

• Groups 3-5 (Female participants only): Must be non-pregnant (as demonstrated by anegative urine pregnancy test), and practice continuous effective contraception forthe 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 permanentresidence in the study area.

• Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or infants with Z-score ofweight-for-age within ±2SD.

Exclusion Criteria:

• Clinically significant congenital abnormalities as judged by the PI or otherdelegated individual

• Clinically significant history of skin disorder (psoriasis, contact dermatitisetc.), allergy, cardiovascular disease, respiratory disease, endocrine disorder,liver disease, renal disease, gastrointestinal disease and neurological illness asjudged by the PI or other delegated individual.

• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIVinfection; asplenia; recurrent, severe infections and chronic (more than 14 days)immunosuppressant medication within the past 6 months (inhaled and topical steroidsare allowed).

• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma insitu).

• History of allergic disease or reactions likely to be exacerbated by any componentof 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 thePI or other delegated individual.

• Administration of immunoglobulins and/or any blood products within the three monthspreceding the planned administration of the vaccine candidate.

• Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of anyother vaccine within 30 days following each study vaccination. This excludesCOVID-19 vaccines, which should not be received between 14 days before to 7 daysafter any study vaccination, and EPI vaccines (for infants), which should not bereceived 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 investigationalproduct in the 30 days preceding enrolment in adults or at any time for infants, orplanned 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 wouldincrease 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 thecourse of the trial.

• Scheduled elective surgery or other procedures requiring general anaesthesia duringthe trial.

• Any other significant disease, disorder or situation which, in the opinion of theInvestigator, may either put the participants at risk because of participation inthe trial, or may influence the result of the trial, or the participant's ability toparticipate in the trial.

Vaccination and re-vaccination exclusion criteria

The following events associated with vaccine immunisation constitute absolute contraindications to further administration of vaccine. If any of these events occur during the study, the participant must be withdrawn and followed until resolution of the event, as with any adverse event:

• Anaphylactic reaction following administration of vaccine.

• Pregnancy. The following adverse events constitute contraindications toadministration of vaccine at that point in time; if any one of these adverse eventsoccurs at the time scheduled for vaccination, the participant may be vaccinated at alater date, or withdrawn at the discretion of the Investigator.

The participant must be followed until resolution of the event as with any adverse event:

• Acute disease at the time of administration of the IP (acute disease is defined asthe presence of a moderate or severe illness with or without fever or symptomssuggestive of possible COVID-19 disease). All vaccines can be administered topersons with a minor illness such as diarrhoea or mild upper respiratory infectionwithout fever, i.e. axillary temperature < 37.5°C.

• Temperature of >37.5°C (99.5°F) at the time of vaccination.

• Confirmed current COVID-19 infection, defined as ongoing symptoms with positiveCOVID-19 PCR swab or rapid antigen test taken during current illness or positiveCOVID-19 PCR swab or rapid antigen test within preceding 7 days without symptoms.Vaccinations will be delayed by a minimum of 7 days from the date of the firstpositive COVID-19 PCR swab, as long as symptoms are improving or resolved and thereis no fever. It will be at the discretion of the Investigator to withdraw aparticipant if they develop severe COVID-19 disease.