Imperial College London

ProfessorRobinShattock

Faculty of MedicineDepartment of Infectious Disease

Chair in Mucosal Infection and Immunity
 
 
 
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Contact

 

+44 (0)20 7594 5206r.shattock

 
 
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Location

 

453Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Aldon:2018:10.1016/j.celrep.2018.08.051,
author = {Aldon, Y and McKay, PF and Allen, J and Ozorowski, G and Levai, RF and Tolazzi, M and Rogers, P and He, L and de, Val N and Fabian, K and Scarlatti, G and Zhu, J and Ward, AB and Crispin, M and Shattock, RJ},
doi = {10.1016/j.celrep.2018.08.051},
journal = {Cell Reports},
pages = {3324--3338.e5},
title = {Rational design of DNA-expressed stabilized native-like HIV-1 envelope trimers},
url = {http://dx.doi.org/10.1016/j.celrep.2018.08.051},
volume = {24},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for antibody-based prophylactic vaccines. The generation of broadly neutralizing antibodies (bNAb) likely requires the appropriate presentation of stabilized trimers preventing exposure of non-neutralizing antibody (nNAb) epitopes. We designed a series of membrane-bound Envs with increased trimer stability through the introduction of key stabilization mutations. We derived a stabilized HIV-1 trimer, ConSOSL.UFO.750, which displays a dramatic reduction in nNAb binding while maintaining high quaternary and MPER-specific bNAb binding. Its soluble counterpart, ConSOSL.UFO.664, displays similar antigenicity, and its native-like Env structure is confirmed by negative stain-EM and glycosylation profiling of the soluble ConSOSL.UFO.664 trimer. A rabbit immunization study demonstrated that the ConSOSL.UFO.664 can induce autologous tier 2 neutralization. We have successfully designed a stabilized native-like Env trimer amenable to nucleic acid or viral vector-based vaccination strategies.
AU - Aldon,Y
AU - McKay,PF
AU - Allen,J
AU - Ozorowski,G
AU - Levai,RF
AU - Tolazzi,M
AU - Rogers,P
AU - He,L
AU - de,Val N
AU - Fabian,K
AU - Scarlatti,G
AU - Zhu,J
AU - Ward,AB
AU - Crispin,M
AU - Shattock,RJ
DO - 10.1016/j.celrep.2018.08.051
EP - 3338
PY - 2018///
SN - 2211-1247
SP - 3324
TI - Rational design of DNA-expressed stabilized native-like HIV-1 envelope trimers
T2 - Cell Reports
UR - http://dx.doi.org/10.1016/j.celrep.2018.08.051
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000444924100021&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/63546
VL - 24
ER -