Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZs) has been 
shown to be protective against malaria, but the features of the antibody 
response induced by this treatment remain unclear. To investigate this response 
in detail, we isolated IgM and IgG monoclonal antibodies from Tanzanian 
volunteers who were immunized with repeated injection of Sanaria PfSPZ Vaccine 
and who were found to be protected from controlled human malaria infection with 
infectious homologous PfSPZs. All isolated IgG monoclonal antibodies bound to P. 
falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in 
its N terminus, NANP-repeat region, and C terminus. Strikingly, the most 
effective antibodies, as determined in a humanized mouse model, bound not only 
to the repeat region, but also to a minimal peptide at the PfCSP N-terminal 
junction that is not in the RTS,S vaccine. These dual-specific antibodies were 
isolated from different donors and were encoded by VH3-30 or VH3-33 alleles that 
encode tryptophan or arginine at position 52. Using structural and mutational 
data, we describe the elements required for germline recognition and affinity 
maturation. Our study provides potent neutralizing antibodies and relevant 
information for lineage-targeted vaccine design and immunization strategies.