Infant Malaria Vaccine Schedule Optimization

Inclusion Criteria: * Signed informed consent or thumb-printed and witnessed informed consent obtained from the parent/legal guardian of the infant. * Infants must have been born full-term (at ≥37 weeks of gestation) and \> 2500 grams at birth. * Immunization schedule Cohorts 1, 2, and 3: Male and female infants 42-49 days (inclusive) of age at time of enrollment. * Prior to group randomization, for infants in Cohort 1 randomization to receive vaccine dose 1 (Groups 1 and 2 of R21/MM or placebo, respectively) will occur at 42-49 days of age. Infants in Cohorts 2 and 3 will not be randomized to R21/MM or placebo; placebo will no longer be given. Rather infants in these cohorts will receive open-label R21/MM according to the immunization schedule category to which they have been randomized. Infants in Cohort 2, will receive their open-label R21/MM vaccine dose 1 (Group 3) at 2 months (56-63 days of age). Infants in Cohort 3, will receive their open-label R21/MM vaccine dose 1 (Group 5) at 3 months (84-91 days of age). * The participant's parent/guardian must be willing to avoid travel, particularly in the 28 days after each study vaccination, must confirm willingness to contact the study team in the event of unexpected/unavoidable travel and, for the safety cohort, must confirm availability for the home visits to be conducted by a field worker or nurse to collect solicited AEs over the 7 days (day of vaccination and 6 subsequent days) following each study vaccine. * The participant's parent/guardian must confirm willingness to bring their child to the study clinic / local health care clinic, and capacity to contact the study team in the event the subject has any illnesses or other health concerns during the study. * Participants who the investigator believes that their parent/guardian can and will comply with the requirements of the protocol (e.g. return for follow-up visits) may be enrolled in the study. Exclusion Criteria: • Acute disease at the time of enrolment (acute disease is defined as the presence of a moderate or severe illness with or without fever). This does not include minor illnesses such as diarrhea, mild upper respiratory infection, without low-grade febrile illness, i.e. axillary temperature \< 37.5°C or tympanic temperature \< 38°C. (Note: In case of acute disease, participants may be re-assessed by a study physician for resolution of the condition and enrolled if eligible and still within the visit window). * Clinically significant pulmonary, cardiovascular, gastrointestinal, endocrine, neurological, skin, hepatic or renal functional abnormality, as determined by medical history, physical examination or laboratory tests 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. * At time of enrollment, any infant who has received any dose of the hexavalent/pentavalent vaccines, pneumococcal vaccine, rotavirus vaccine, IPV or has received more than one dose of oral polio virus or more than one dose of hepatitis B vaccine. * Weight-for-length/height Z score of less than -3 or other clinical signs of malnutrition. * Infant with major congenital defects. * The infant has anaemia associated with clinical signs of symptoms of decompensation, or a haemoglobin of ≤ 5.0 g/dL. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. * Any confirmed or suspected immunosuppressive or immunodeficient state (including HIV or asplenia) or known maternal HIV infection (no HIV testing will be routinely done by the study team). * Administration of immunoglobulins and/or any blood products/blood transfusion from birth to time of planned administration of the vaccine candidate. * Previous vaccination of participant or biological mother with a malaria vaccine. * Participation in another research study involving receipt of an investigational product or planned use during the study period. * Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.