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Antibodies against the NANP repeat of circumsporozoite protein (CSP), the major surface antigen of Plasmodium falciparum (Pf) sporozoites, can protect from malaria in animal models but protective humoral immunity is difficult to induce in humans. Here we cloned and characterized rare affinity-matured human NANP-reactive memory B cell antibodies elicited by natural Pf exposure that potently inhibited parasite transmission and development in vivo. We unveiled the molecular details of antibody binding to two distinct protective epitopes within the NANP repeat. NANP repeat recognition was largely mediated by germline encoded and immunoglobulin (Ig) heavy-chain complementarity determining region 3 (HCDR3) residues, whereas affinity maturation contributed predominantly to stabilizing the antigen-binding site conformation. Combined, our findings illustrate the power of exploring human anti-CSP antibody responses to develop tools for malaria control in the mammalian and the mosquito vector and provide a molecular basis for the structure-based design of next-generation CSP malaria vaccines.
Pubmed ID: 29195810 RIS Download
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Vector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.
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View all literature mentionsThis unknown targets Mouse IgG (H+L)
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View all literature mentionsThis unknown targets Human IgG, Fc? Fragment Specific
View all literature mentionsThis unknown targets Human IgG, Fc? Fragment Specific
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View all literature mentionsThis unknown targets Human IgG, Fc? Fragment Specific
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View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsThis polyclonal secondary targets IgG (H+L) Poly-HRP
View all literature mentionsThis monoclonal targets CD21
View all literature mentionsThis unknown targets Human IgG, Fc? Fragment Specific
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
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