Infant Malaria Vaccine Schedule Optimization

The R21/Matrix-M (R21/MM) vaccine has been recommended by the World Health Organization (WHO) to prevent clinical malaria in young children living in moderate to high transmission areas of Sub-Saharan Africa. R21/MM is based on the circumsporozoite protein (CSP) targeting the pre-erythrocytic stage of Plasmodium falciparum. R21/MM elicits high levels of antibodies against the central repeat (Asn-Ala-Asn-Pro \[NANP\]) of the circumsporozoite protein (CSP) which has been shown to correlate with protection. Currently, R21/MM is recommended to be delivered to young children starting at 5-6 months of age with 3 doses given at monthly intervals, however, there are no existing Essential Programme on Immunization (EPI) vaccine visits scheduled at these ages.

We plan to evaluate, using the R21/MM malaria vaccine as a model system, how age at first vaccine dose and time intervals between doses modify the immunogenicity of the vaccine and the ensuant efficacy in protecting infants against clinical Plasmodium falciparum malaria.

Healthy male or female infants 6 to 7 weeks of age will be randomized to one of three different immunization schedule cohorts: a) a "compressed" conventional schedule at 6-10-14 weeks of age; b) a "relaxed" schedule at 2-4-6 months of age; c) a "relaxed" schedule at 3-6-9 months of age. Participants in each immunization schedule cohort will be randomized in a ratio of 3:1 to receive 4 doses of either R21/MM or placebo with a 4th dose to be administered at 15 months of age.

Infants randomized to the respective immunization schedule categories will receive co-administered routine EPI vaccines. The study will include the provision of a three dose R21/MM compressed schedule to all participants randomized to the placebo arms upon completion of the study at Month 27 of life.