Imperial College London
Portrait Picture

ProfessorPaulKellam

Faculty of Medicine, Department of Infectious Disease

Professor of Virus Genomics
 
 
 
//

Contact

 

p.kellam

 
 
//

Location

 

460Wright Fleming WingSt Mary's Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Oyen:2020:10.1371/journal.ppat.1008373,
author = {Oyen, D and Torres, JL and Aoto, PC and Flores-Garcia, Y and Binter, S and Pholcharee, T and Carroll, S and Reponen, S and Wash, R and Liang, Q and King, CR and Emerling, D and Kellam, P and Zavala, F and Ward, AB and Wilson, IA and Lemiale, F and Locke, E and Bradley, A},
doi = {10.1371/journal.ppat.1008373},
journal = {PLoS Pathogens},
pages = {1--22},
title = {Structure and mechanism of monoclonal antibody binding to the junctional epitope of Plasmodium falciparum circumsporozoite protein},
url = {http://dx.doi.org/10.1371/journal.ppat.1008373},
volume = {16},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 of protection against sporozoite challenge in mouse liver burden models, suggesting that junctional antibody protection might relate to the ability to also cross-react with the NANP repeat region. Our findings indicate that additional efforts are necessary to isolate a true junctional antibody with no or much reduced affinity to the NANP region to elucidate the role of the junctional epitope in protection.
AU  - Oyen,D
AU  - Torres,JL
AU  - Aoto,PC
AU  - Flores-Garcia,Y
AU  - Binter,S
AU  - Pholcharee,T
AU  - Carroll,S
AU  - Reponen,S
AU  - Wash,R
AU  - Liang,Q
AU  - King,CR
AU  - Emerling,D
AU  - Kellam,P
AU  - Zavala,F
AU  - Ward,AB
AU  - Wilson,IA
AU  - Lemiale,F
AU  - Locke,E
AU  - Bradley,A
DO  - 10.1371/journal.ppat.1008373
EP  - 22
PY  - 2020///
SN  - 1553-7366
SP  - 1
TI  - Structure and mechanism of monoclonal antibody binding to the junctional epitope of Plasmodium falciparum circumsporozoite protein
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1008373
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000523706200002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008373
UR  - http://hdl.handle.net/10044/1/81513
VL  - 16
ER  -
Download