Imperial College London
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Dr Hannah M Cheeseman

Faculty of Medicine, Department of Infectious Disease

Postdoctoral Researcher & Clinical Trials Laboratory Manager
 
 
 
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Contact

 

+44 (0)20 7594 2540hannah.cheeseman

 
 
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Location

 

452 - Shattock GroupNorfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Cheeseman:2016:10.1128/JVI.01762-16,
author = {Cheeseman, HM and Olejniczak, NJ and Rogers, PM and Evans, AB and King, DFL and Ziprin, P and Liao, H-X and Haynes, BF and Shattock, RJ},
doi = {10.1128/JVI.01762-16},
journal = {Journal of Virology},
title = {Broadly neutralizing antibodies display potential for prevention of HIV-1 infection of mucosal tissue superior to that of nonneutralizing antibodies},
url = {http://dx.doi.org/10.1128/JVI.01762-16},
volume = {91},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Definition of the key parameters mediating effective antibody blocking of HIV-1 acquisition within mucosal tissue may prove critical to effective vaccine development and the prophylactic use of monoclonal antibodies. Although direct antibody-mediated neutralization is highly effective against cell-free virus, antibodies targeting different sites of envelope vulnerability may display differential activity against mucosal infection. Nonneutralizing antibodies (nnAbs) may also impact mucosal transmission events through Fc-gamma receptor (FcγR)-mediated inhibition. In this study, a panel of broadly neutralizing antibodies (bnAbs) and nnAbs, including those associated with protection in the RV144 vaccine trial, were screened for the ability to block HIV-1 acquisition and replication across a range of cellular and mucosal tissue models. Neutralization potency, as determined by the TZM-bl infection assay, did not fully predict activity in mucosal tissue. CD4-binding site (CD4bs)-specific bnAbs, in particular VRC01, were consistent in blocking HIV-1 infection across all cellular and tissue models. Membrane-proximal external region (MPER) (2F5) and outer domain glycan (2G12) bnAbs were also efficient in preventing infection of mucosal tissues, while the protective efficacy of bnAbs targeting V1-V2 glycans (PG9 and PG16) was more variable. In contrast, nnAbs alone and in combinations, while active in a range of cellular assays, were poorly protective against HIV-1 infection of mucosal tissues. These data suggest that tissue resident effector cell numbers and low FcγR expression may limit the potential of nnAbs to prevent establishment of the initial foci of infection. The solid protection provided by specific bnAbs clearly demonstrates their superior potential over that of nonneutralizing antibodies for preventing HIV-1 infection at the mucosal portals of infection.IMPORTANCE Key parameters mediating effective antibody blocking of HIV-1 acquisition within mucosal
AU  - Cheeseman,HM
AU  - Olejniczak,NJ
AU  - Rogers,PM
AU  - Evans,AB
AU  - King,DFL
AU  - Ziprin,P
AU  - Liao,H-X
AU  - Haynes,BF
AU  - Shattock,RJ
DO  - 10.1128/JVI.01762-16
PY  - 2016///
SN  - 1098-5514
TI  - Broadly neutralizing antibodies display potential for prevention of HIV-1 infection of mucosal tissue superior to that of nonneutralizing antibodies
T2  - Journal of Virology
UR  - http://dx.doi.org/10.1128/JVI.01762-16
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000393189200027&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/44713
VL  - 91
ER  -
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