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Article: Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41

TitleIdentification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41
Authors
Issue Date2012
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2012, v. 7 n. 9, e44241 How to Cite?
AbstractIdentification of broadly cross-reactive HIV-1-neutralizing antibodies (bnAbs) may assist vaccine immunogen design. Here we report a novel human monoclonal antibody (mAb), designated m43, which co-targets the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein (Env). M43 bound to recombinant gp140 s from various primary isolates, to membrane-associated Envs on transfected cells and HIV-1 infected cells, as well as to recombinant gp120 s and gp41 fusion intermediate structures containing N-trimer structure, but did not bind to denatured recombinant gp140 s and the CD4 binding site (CD4bs) mutant, gp120 D368R, suggesting that the m43 epitope is conformational and overlaps the CD4bs on gp120 and the N-trimer structure on gp41. M43 neutralized 34% of the HIV-1 primary isolates from different clades and all the SHIVs tested in assays based on infection of peripheral blood mononuclear cells (PBMCs) by replication-competent virus, but was less potent in cell line-based pseudovirus assays. In contrast to CD4, m43 did not induce Env conformational changes upon binding leading to exposure of the coreceptor binding site, enhanced binding of mAbs 2F5 and 4E10 specific for the membrane proximal external region (MPER) of gp41 Envs, or increased gp120 shedding. The overall modest neutralization activity of m43 is likely due to the limited binding of m43 to functional Envs which could be increased by antibody engineering if needed. M43 may represent a new class of bnAbs targeting conformational epitopes overlapping structures on both gp120 and gp41. Its novel epitope and possibly new mechanism(s) of neutralization could helpdesign improved vaccine immunogens and candidate therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/159709
ISSN
2014 Impact Factor: 3.234
2014 SCImago Journal Rankings: 1.300
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, Men_US
dc.contributor.authorYuan, Ten_US
dc.contributor.authorLi, Jen_US
dc.contributor.authorBorges, ARen_US
dc.contributor.authorWatkins, JDen_US
dc.contributor.authorGuenaga, Jen_US
dc.contributor.authorYang, Zen_US
dc.contributor.authorWang, Yen_US
dc.contributor.authorWilson, Ren_US
dc.contributor.authorLi, Yen_US
dc.contributor.authorPolonis, VRen_US
dc.contributor.authorPincus, SHen_US
dc.contributor.authorRuprecht, RMen_US
dc.contributor.authorDimitrov, DSen_US
dc.date.accessioned2012-08-16T05:54:47Z-
dc.date.available2012-08-16T05:54:47Z-
dc.date.issued2012en_US
dc.identifier.citationPLoS One, 2012, v. 7 n. 9, e44241en_US
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/159709-
dc.description.abstractIdentification of broadly cross-reactive HIV-1-neutralizing antibodies (bnAbs) may assist vaccine immunogen design. Here we report a novel human monoclonal antibody (mAb), designated m43, which co-targets the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein (Env). M43 bound to recombinant gp140 s from various primary isolates, to membrane-associated Envs on transfected cells and HIV-1 infected cells, as well as to recombinant gp120 s and gp41 fusion intermediate structures containing N-trimer structure, but did not bind to denatured recombinant gp140 s and the CD4 binding site (CD4bs) mutant, gp120 D368R, suggesting that the m43 epitope is conformational and overlaps the CD4bs on gp120 and the N-trimer structure on gp41. M43 neutralized 34% of the HIV-1 primary isolates from different clades and all the SHIVs tested in assays based on infection of peripheral blood mononuclear cells (PBMCs) by replication-competent virus, but was less potent in cell line-based pseudovirus assays. In contrast to CD4, m43 did not induce Env conformational changes upon binding leading to exposure of the coreceptor binding site, enhanced binding of mAbs 2F5 and 4E10 specific for the membrane proximal external region (MPER) of gp41 Envs, or increased gp120 shedding. The overall modest neutralization activity of m43 is likely due to the limited binding of m43 to functional Envs which could be increased by antibody engineering if needed. M43 may represent a new class of bnAbs targeting conformational epitopes overlapping structures on both gp120 and gp41. Its novel epitope and possibly new mechanism(s) of neutralization could helpdesign improved vaccine immunogens and candidate therapeutics.-
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPLoS Oneen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleIdentification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41en_US
dc.typeArticleen_US
dc.identifier.emailZhang, M: zhangmy@hku.hken_US
dc.identifier.emailLi, J: joyli@hku.hken_US
dc.identifier.emailYang, Z: yangzack@hku.hk-
dc.identifier.emailDimitrov, DS: dimiter.dimitrov@nih.gov-
dc.identifier.authorityZhang, M=rp01409en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0044241-
dc.identifier.pmid22970187-
dc.identifier.hkuros202162en_US
dc.identifier.volume7en_US
dc.identifier.issue9-
dc.identifier.isiWOS:000308748400013-
dc.publisher.placeUnited States-
dc.customcontrol.immutablesml 130322-

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