Structure and mechanism of monoclonal antibody binding to the junctional epitope of Plasmodium falciparum circumsporozoite protein

PLoS Pathogens
David OyenIan A Wilson

Abstract

Lasting protection has long been a goal for malaria vaccines. The major surface antigen on Plasmodium falciparum sporozoites, the circumsporozoite protein (PfCSP), has been an attractive target for vaccine development and most protective antibodies studied to date interact with the central NANP repeat region of PfCSP. However, it remains unclear what structural and functional characteristics correlate with better protection by one antibody over another. Binding to the junctional region between the N-terminal domain and central NANP repeats has been proposed to result in superior protection: this region initiates with the only NPDP sequence followed immediately by NANP. Here, we isolated antibodies in Kymab mice immunized with full-length recombinant PfCSP and two protective antibodies were selected for further study with reactivity against the junctional region. X-ray and EM structures of two monoclonal antibodies, mAb667 and mAb668, shed light on their differential affinity and specificity for the junctional region. Importantly, these antibodies also bind to the NANP repeat region with equal or better affinity. A comparison with an NANP-only binding antibody (mAb317) revealed roughly similar but statistically distinct levels o...Continue Reading

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Citations

Aug 14, 2020·The Journal of Experimental Medicine·Elaine ThaiElena A Levashina
Nov 27, 2020·Microbiology and Molecular Biology Reviews : MMBR·Gunnar Lindahl

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Methods Mentioned

BETA
electron microscopy
transgenic
Assay
ELISA
X-ray
electron
light scattering
ISA
transfection
size-exclusion chromatography

Software Mentioned

ASTRA
DogPicker
2000
PROPKA
IgBlast
refine
Octet QK384 Data Analysis
Ambertools
SoDA
PIGSPro

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