Plasmodium falciparum remains a major global health challenge, and current vaccines provide only partial and short-lived protection. Through longitudinal functional antibody and B-cell repertoire analyses in both mice and humans, we track the evolution of responses to leading P. falciparum vaccine candidates. These studies reveal the molecular and cellular mechanisms that shape the development of protective humoral immunity, including the clonal dynamics, affinity maturation pathways, and epitope specificities associated with effective antibody-mediated protection. I will highlight how these insights into B-cell biology inform rational immunogen design and guide the development of next-generation malaria vaccines.