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Article: Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody

TitleIdentification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody
Authors
Issue Date2004
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal Of Virology, 2004, v. 78 n. 17, p. 9233-9242 How to Cite?
AbstractThe identification and characterization of new human monoclonal antibodies (hMAbs) able to neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates from different subtypes may help in our understanding of the mechanisms of virus entry and neutralization and in the development of entry inhibitors and vaccines. For enhanced selection of broadly cross-reactive antibodies, soluble HIV-1 envelope glycoproteins (Envs proteins) from two isolates complexed with two-domain soluble CD4 (sCD4) were alternated during panning of a phage-displayed human antibody library; these two Env proteins (89.6 and IIIB gp140s), and one additional Env (JR-FL gp120) alone and complexed with sCD4 were used for screening. An antibody with relatively long HCDR3 (17 residues), designated m14, was identified that bound to all antigens and neutralized heterologous HIV-1 isolates in multiple assay formats. Fab m14 potently neutralized selected well-characterized subtype B isolates, including JRCSF, 89.6, IIIB, and Yu2. Immunoglobulin G1 (IgG1) m14 was more potent than Fab m14 and neutralized 7 of 10 other clade B isolates; notably, although the potency was on average significantly lower than that of IgG1 b12, IgG1 m14 neutralized two of the isolates with significantly lower 50% inhibitory concentrations than did IgG1 b12. IgG1 m14 neutralized four of four selected clade C isolates with potency higher than that of IgG1 b12. It also neutralized 7 of 17 clade C isolates from southern Africa that were difficult to neutralize with other hMAbs and sCD4. IgG1 m14 neutralized four of seven primary HIV-1 isolates from other clades (A, D, E, and F) much more efficiently than did IgG1 b12; for the other three isolates, IgG b12 was much more potent. Fab m14 bound with high (nanomolar range) affinity to gp120 and gp140 from various isolates; its binding was reduced by soluble CD4 and antibodies recognizing the CD4 binding site (CD4bs) on gp120, and its footprint as defined by alanine-scanning mutagenesis overlaps that of b12. These results suggest that m14 is a novel CD4bs cross-reactive HIV-1-neutralizing antibody that exhibits a different inhibitory profile compared to the only known potent broadly neutralizing CD4bs human antibody, b12, and may have implications for our understanding of the mechanisms of immune evasion and for the development of inhibitors and vaccines.
Persistent Identifierhttp://hdl.handle.net/10722/157515
ISSN
2015 Impact Factor: 4.606
2015 SCImago Journal Rankings: 3.347
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhang, MYen_US
dc.contributor.authorXiao, Xen_US
dc.contributor.authorSidorov, IAen_US
dc.contributor.authorChoudhry, Ven_US
dc.contributor.authorCham, Fen_US
dc.contributor.authorZhang, PFen_US
dc.contributor.authorBouma, Pen_US
dc.contributor.authorZwick, Men_US
dc.contributor.authorChoudhary, Aen_US
dc.contributor.authorMontefiori, DCen_US
dc.contributor.authorBroder, CCen_US
dc.contributor.authorBurton, DRen_US
dc.contributor.authorQuinnan Jr, GVen_US
dc.contributor.authorDimitrov, DSen_US
dc.date.accessioned2012-08-08T08:50:47Z-
dc.date.available2012-08-08T08:50:47Z-
dc.date.issued2004en_US
dc.identifier.citationJournal Of Virology, 2004, v. 78 n. 17, p. 9233-9242en_US
dc.identifier.issn0022-538Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/157515-
dc.description.abstractThe identification and characterization of new human monoclonal antibodies (hMAbs) able to neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates from different subtypes may help in our understanding of the mechanisms of virus entry and neutralization and in the development of entry inhibitors and vaccines. For enhanced selection of broadly cross-reactive antibodies, soluble HIV-1 envelope glycoproteins (Envs proteins) from two isolates complexed with two-domain soluble CD4 (sCD4) were alternated during panning of a phage-displayed human antibody library; these two Env proteins (89.6 and IIIB gp140s), and one additional Env (JR-FL gp120) alone and complexed with sCD4 were used for screening. An antibody with relatively long HCDR3 (17 residues), designated m14, was identified that bound to all antigens and neutralized heterologous HIV-1 isolates in multiple assay formats. Fab m14 potently neutralized selected well-characterized subtype B isolates, including JRCSF, 89.6, IIIB, and Yu2. Immunoglobulin G1 (IgG1) m14 was more potent than Fab m14 and neutralized 7 of 10 other clade B isolates; notably, although the potency was on average significantly lower than that of IgG1 b12, IgG1 m14 neutralized two of the isolates with significantly lower 50% inhibitory concentrations than did IgG1 b12. IgG1 m14 neutralized four of four selected clade C isolates with potency higher than that of IgG1 b12. It also neutralized 7 of 17 clade C isolates from southern Africa that were difficult to neutralize with other hMAbs and sCD4. IgG1 m14 neutralized four of seven primary HIV-1 isolates from other clades (A, D, E, and F) much more efficiently than did IgG1 b12; for the other three isolates, IgG b12 was much more potent. Fab m14 bound with high (nanomolar range) affinity to gp120 and gp140 from various isolates; its binding was reduced by soluble CD4 and antibodies recognizing the CD4 binding site (CD4bs) on gp120, and its footprint as defined by alanine-scanning mutagenesis overlaps that of b12. These results suggest that m14 is a novel CD4bs cross-reactive HIV-1-neutralizing antibody that exhibits a different inhibitory profile compared to the only known potent broadly neutralizing CD4bs human antibody, b12, and may have implications for our understanding of the mechanisms of immune evasion and for the development of inhibitors and vaccines.en_US
dc.languageengen_US
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/en_US
dc.relation.ispartofJournal of Virologyen_US
dc.subject.meshAlanine - Genetics - Metabolismen_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshAntibodies, Monoclonal - Genetics - Immunology - Isolation & Purificationen_US
dc.subject.meshAntigens, Cd4 - Immunologyen_US
dc.subject.meshBacteriophages - Geneticsen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshBiosensing Techniquesen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCross Reactions - Immunologyen_US
dc.subject.meshEpitopes - Chemistry - Genetics - Immunologyen_US
dc.subject.meshGene Products, Env - Immunologyen_US
dc.subject.meshGenomicsen_US
dc.subject.meshHiv Antibodies - Genetics - Immunology - Isolation & Purificationen_US
dc.subject.meshHiv Envelope Protein Gp120 - Immunologyen_US
dc.subject.meshHiv-1 - Classification - Immunologyen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoglobulin Fab Fragments - Genetics - Immunology - Isolation & Purificationen_US
dc.subject.meshImmunoglobulin G - Genetics - Immunology - Isolation & Purificationen_US
dc.subject.meshKineticsen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutagenesis - Geneticsen_US
dc.subject.meshNeutralization Testsen_US
dc.subject.meshPeptide Libraryen_US
dc.subject.meshEnv Gene Products, Human Immunodeficiency Virusen_US
dc.titleIdentification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibodyen_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.doi10.1128/JVI.78.17.9233-9242.2004en_US
dc.identifier.pmid15308718-
dc.identifier.scopuseid_2-s2.0-4143088167en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-4143088167&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume78en_US
dc.identifier.issue17en_US
dc.identifier.spage9233en_US
dc.identifier.epage9242en_US
dc.identifier.isiWOS:000223386600027-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridZhang, MY=35316639300en_US
dc.identifier.scopusauthoridXiao, X=7402168892en_US
dc.identifier.scopusauthoridSidorov, IA=7005186545en_US
dc.identifier.scopusauthoridChoudhry, V=8530897500en_US
dc.identifier.scopusauthoridCham, F=6507851729en_US
dc.identifier.scopusauthoridZhang, PF=7404160106en_US
dc.identifier.scopusauthoridBouma, P=7003730370en_US
dc.identifier.scopusauthoridZwick, M=8105899100en_US
dc.identifier.scopusauthoridChoudhary, A=8743351100en_US
dc.identifier.scopusauthoridMontefiori, DC=7005651585en_US
dc.identifier.scopusauthoridBroder, CC=7004376461en_US
dc.identifier.scopusauthoridBurton, DR=7401577043en_US
dc.identifier.scopusauthoridQuinnan Jr, GV=7006729933en_US
dc.identifier.scopusauthoridDimitrov, DS=7202564539en_US
dc.identifier.citeulike1460612-

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