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bioRxiv · 10.1101/2024.01.18.574923

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

Beutler, N.·Garcia, E.·Lai, Y.-C.·Ndihokubwayo, J.·Gambuzza, K.·Zhao, J.·Burton, D.·Rogers, T.
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Abstract

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.

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Beutler, N., Garcia, E., Lai, Y.-C., Ndihokubwayo, J., Gambuzza, K., Zhao, J., Burton, D., Rogers, T.. 2024-01-20. The N-terminus of Plasmodium falciparum Circumsporozoite Protein Contains Three Non-Overlapping Murine B-cell Epitope Regions. https://doi.org/10.1101/2024.01.18.574923

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