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Article: Increased efficacy of HIV-1 neutralization by antibodies at low CCR5 surface concentration

TitleIncreased efficacy of HIV-1 neutralization by antibodies at low CCR5 surface concentration
Authors
Issue Date2006
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description
Citation
Biochemical And Biophysical Research Communications, 2006, v. 348 n. 3, p. 1107-1115 How to Cite?
AbstractIt has been observed that some antibodies, including the CD4-induced (CD4i) antibody IgG X5 and the gp41-specific antibody IgG 2F5, exhibit higher neutralizing activity in PBMC-based assays than in cell line based assays [J.M. Binley, T. Wrin, B. Korber, M.B. Zwick, M. Wang, C. Chappey, G. Stiegler, R. Kunert, S. Zolla-Pazner, H. Katinger, C.J. Petropoulos, D.R. Burton, Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies, J. Virol. 78 (2004) 13232-13252]. It has been hypothesized that the lower CCR5 concentration on the surface of the CD4 T lymphocytes compared to that on cell lines used for the neutralization assays could be a contributing factor to the observed differences in neutralizing activity. To test this hypothesis and to further elucidate the contribution of CCR5 concentration differences on antibody neutralizing activity, we used a panel of HeLa cell lines with well-defined and differential surface concentrations of CCR5 and CD4 in a pseudovirus-based assay. We observed that the CCR5 cell surface concentration but not the CD4 concentration had a significant effect on the inhibitory activity of X5 and several other CD4i antibodies including 17b and m9, as well as that of the gp41-specifc antibodies 2F5 and 4E10 but not on that of the CD4 binding site antibody (CD4bs), b12. The 50% inhibitory concentration (IC50) decreased up to two orders of magnitude in cell lines with low CCR5 concentration corresponding to that in CD4 T cells used in PBMC-based assays (about 103 per cell) compared to cell lines with high CCR5 concentration (about 104 or more). Our results suggest that the CCR5 cell surface concentration could be a contributing factor to the high neutralizing activities of some antibodies in PBMC-based-assays but other factors could also play an important role. These findings could have implications for development of vaccine immunogens based on the epitopes of X5 and other CD4i antibodies, for elucidation of the mechanisms of HIV-1 neutralization by antibodies, and for design of novel therapeutic approaches.
Persistent Identifierhttp://hdl.handle.net/10722/157454
ISSN
2015 Impact Factor: 2.371
2015 SCImago Journal Rankings: 1.152
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChoudhry, Ven_US
dc.contributor.authorZhang, MYen_US
dc.contributor.authorHarris, Ien_US
dc.contributor.authorSidorov, IAen_US
dc.contributor.authorVu, Ben_US
dc.contributor.authorDimitrov, ASen_US
dc.contributor.authorFouts, Ten_US
dc.contributor.authorDimitrov, DSen_US
dc.date.accessioned2012-08-08T08:50:06Z-
dc.date.available2012-08-08T08:50:06Z-
dc.date.issued2006en_US
dc.identifier.citationBiochemical And Biophysical Research Communications, 2006, v. 348 n. 3, p. 1107-1115en_US
dc.identifier.issn0006-291Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/157454-
dc.description.abstractIt has been observed that some antibodies, including the CD4-induced (CD4i) antibody IgG X5 and the gp41-specific antibody IgG 2F5, exhibit higher neutralizing activity in PBMC-based assays than in cell line based assays [J.M. Binley, T. Wrin, B. Korber, M.B. Zwick, M. Wang, C. Chappey, G. Stiegler, R. Kunert, S. Zolla-Pazner, H. Katinger, C.J. Petropoulos, D.R. Burton, Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies, J. Virol. 78 (2004) 13232-13252]. It has been hypothesized that the lower CCR5 concentration on the surface of the CD4 T lymphocytes compared to that on cell lines used for the neutralization assays could be a contributing factor to the observed differences in neutralizing activity. To test this hypothesis and to further elucidate the contribution of CCR5 concentration differences on antibody neutralizing activity, we used a panel of HeLa cell lines with well-defined and differential surface concentrations of CCR5 and CD4 in a pseudovirus-based assay. We observed that the CCR5 cell surface concentration but not the CD4 concentration had a significant effect on the inhibitory activity of X5 and several other CD4i antibodies including 17b and m9, as well as that of the gp41-specifc antibodies 2F5 and 4E10 but not on that of the CD4 binding site antibody (CD4bs), b12. The 50% inhibitory concentration (IC50) decreased up to two orders of magnitude in cell lines with low CCR5 concentration corresponding to that in CD4 T cells used in PBMC-based assays (about 103 per cell) compared to cell lines with high CCR5 concentration (about 104 or more). Our results suggest that the CCR5 cell surface concentration could be a contributing factor to the high neutralizing activities of some antibodies in PBMC-based-assays but other factors could also play an important role. These findings could have implications for development of vaccine immunogens based on the epitopes of X5 and other CD4i antibodies, for elucidation of the mechanisms of HIV-1 neutralization by antibodies, and for design of novel therapeutic approaches.en_US
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/descriptionen_US
dc.relation.ispartofBiochemical and Biophysical Research Communicationsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshHiv Antibodies - Physiologyen_US
dc.subject.meshHiv Infections - Immunology - Metabolismen_US
dc.subject.meshHiv-1 - Immunologyen_US
dc.subject.meshHela Cellsen_US
dc.subject.meshHumansen_US
dc.subject.meshNeutralization Testsen_US
dc.subject.meshReceptors, Ccr5 - Metabolismen_US
dc.titleIncreased efficacy of HIV-1 neutralization by antibodies at low CCR5 surface concentrationen_US
dc.typeArticleen_US
dc.identifier.emailZhang, MY:zhangmy@hku.hken_US
dc.identifier.authorityZhang, MY=rp01409en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.bbrc.2006.07.163en_US
dc.identifier.pmid16904645-
dc.identifier.scopuseid_2-s2.0-33747421769en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33747421769&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume348en_US
dc.identifier.issue3en_US
dc.identifier.spage1107en_US
dc.identifier.epage1115en_US
dc.identifier.isiWOS:000240166500045-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChoudhry, V=8530897500en_US
dc.identifier.scopusauthoridZhang, MY=35316639300en_US
dc.identifier.scopusauthoridHarris, I=14070327900en_US
dc.identifier.scopusauthoridSidorov, IA=7005186545en_US
dc.identifier.scopusauthoridVu, B=7003942875en_US
dc.identifier.scopusauthoridDimitrov, AS=7101600999en_US
dc.identifier.scopusauthoridFouts, T=6603607043en_US
dc.identifier.scopusauthoridDimitrov, DS=7202564539en_US

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