Imperial College London
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ProfessorPaulKellam

Faculty of Medicine, Department of Infectious Disease

Professor of Virus Genomics
 
 
 
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Contact

 

p.kellam

 
 
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Location

 

460Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Scally:2017:10.1038/s41467-017-01924-3,
author = {Scally, SW and McLeod, B and Bosch, A and Miura, K and Liang, Q and Carroll, S and Reponen, S and Nguyen, N and Giladi, E and Ramisch, S and Yusibov, V and Bradley, A and Lemiale, F and Schief, WR and Emerling, D and Kellam, P and King, CR and Julien, J-P},
doi = {10.1038/s41467-017-01924-3},
journal = {Nature Communications},
title = {Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25},
url = {http://dx.doi.org/10.1038/s41467-017-01924-3},
volume = {8},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens.
AU  - Scally,SW
AU  - McLeod,B
AU  - Bosch,A
AU  - Miura,K
AU  - Liang,Q
AU  - Carroll,S
AU  - Reponen,S
AU  - Nguyen,N
AU  - Giladi,E
AU  - Ramisch,S
AU  - Yusibov,V
AU  - Bradley,A
AU  - Lemiale,F
AU  - Schief,WR
AU  - Emerling,D
AU  - Kellam,P
AU  - King,CR
AU  - Julien,J-P
DO  - 10.1038/s41467-017-01924-3
PY  - 2017///
SN  - 2041-1723
TI  - Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-017-01924-3
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000415323700015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/70143
VL  - 8
ER  -
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