The N-terminus of Plasmodium falciparum Circumsporozoite Protein Contains Three Non-Overlapping Murine B-cell Epitope Regions

The generation of an anti-malarial vaccine that produces broad, potent, and durable responses is highly desirable to control the burden of Plasmodium falciparum disease. Current vaccines have offered modest efficacy ranging from 50%-70%, likely associated with antibody responses that are relatively short lived and strain specific. Currently approved malaria vaccines, RTS,S and R21, target the repeat region and C-terminal region of Plasmodium falciparum CSP, leaving the N-terminal region of CSP neglected as a target for protective immunogen design. Here, we isolate and express a panel of memory B-cell derived N-terminal CSP-specific monoclonal antibodies (mAbs) from mice immunized with an N-terminal CSP specific immunogen. The characterization of N-terminal specific mAbs including peptide walking and affinity experiments indicate that these antibodies target three distinct sites within the N-terminus of CSP. Site ntCSP-A contains the Region I (RI) cleavage site, which has been previously defined, whereas the remaining two sites are in previously undescribed locations upstream of RI, termed ntCSP-B and ntCSP-C.