This study explores the potential of monoclonal antibodies as a complementary strategy to vaccines in the fight against malaria, particularly for pediatric populations. The researchers characterized the B cell repertoires of 45 RTS,S/AS01 vaccinees and identified monoclonal antibodies with promising antimalarial activity. They generated over 28,000 antibody sequences and tested 481 for binding activity and 125 for in vivo antimalarial activity. The analysis revealed that sequences in *Plasmodium falciparum* circumsporozoite protein (CSP), the target antigen in RTS,S/AS01, may induce immunodominant responses that limit more protective but subdominant responses. Two antibodies, AB-000224 and AB-007088, were selected for clinical development due to their superior binding and in vivo activity. These antibodies were engineered to improve their developability, including manufacturing properties and drug viscosity, to ensure cost-effective distribution to pediatric populations. The optimized antibody, MAM01, is being advanced into clinical trials for its potential to prevent malaria in children living in low- and middle-income countries (LMICs). The study highlights the importance of understanding the humoral response to RTS,S and the role of promiscuous binding in enhancing antibody efficacy.This study explores the potential of monoclonal antibodies as a complementary strategy to vaccines in the fight against malaria, particularly for pediatric populations. The researchers characterized the B cell repertoires of 45 RTS,S/AS01 vaccinees and identified monoclonal antibodies with promising antimalarial activity. They generated over 28,000 antibody sequences and tested 481 for binding activity and 125 for in vivo antimalarial activity. The analysis revealed that sequences in *Plasmodium falciparum* circumsporozoite protein (CSP), the target antigen in RTS,S/AS01, may induce immunodominant responses that limit more protective but subdominant responses. Two antibodies, AB-000224 and AB-007088, were selected for clinical development due to their superior binding and in vivo activity. These antibodies were engineered to improve their developability, including manufacturing properties and drug viscosity, to ensure cost-effective distribution to pediatric populations. The optimized antibody, MAM01, is being advanced into clinical trials for its potential to prevent malaria in children living in low- and middle-income countries (LMICs). The study highlights the importance of understanding the humoral response to RTS,S and the role of promiscuous binding in enhancing antibody efficacy.