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Article: Cross-reactive HIV-1 neutralizing monoclonal antibodies selected by screening of an immune human phage library against an envelope glycoprotein (gp140) isolated from a patient (R2) with broadly HIV-1 neutralizing antibodies

TitleCross-reactive HIV-1 neutralizing monoclonal antibodies selected by screening of an immune human phage library against an envelope glycoprotein (gp140) isolated from a patient (R2) with broadly HIV-1 neutralizing antibodies
Authors
Issue Date2007
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yviro
Citation
Virology, 2007, v. 363 n. 1, p. 79-90 How to Cite?
AbstractElicitation of broadly cross-reactive neutralizing antibodies (bcnAbs) in HIV infections is rare. To test the hypothesis that such antibodies could be elicited by HIV envelope glycoproteins (Envs) with unusual immunogenic properties and to identify novel bcnAbs, we used a soluble Env ectodomain (gp140) from a donor (R2) with high level of bcnAbs as an antigen for panning of an immune phage-displayed antibody library. The panning with the R2 Env resulted in significantly higher number of cross-reactive antibody clones than by using Envs from two other isolates (89.6 and IIIB). Two of the identified human monoclonal antibodies (hmAbs), m22 and m24, had sequences, neutralizing and binding activities similar or identical to those of the gp120-specific bcnAbs m18 and m14. The use of the R2 Env but not other Envs for panning resulted in the identification of a novel gp41-specific hmAb, m46. For several of the tested HIV-1 primary isolates its potency on molar basis was comparable to that of T20. It inhibited entry of primary isolates from different clades with an increased activity for cell lines with low CCR5 surface concentrations. The m46 neutralizing activity against a panel of clade C isolates was significantly higher in an assay based on peripheral blood mononuclear cells (4 out of 5 isolates were neutralized with an IC50 in the range from 1.5 to 25 μg/ml) than in an assay based on a cell line with relatively high concentration of cell-surface-associated CCR5. In contrast to 2F5 and Z13, this antibody did not bind to denatured gp140 and gp41-derived peptides indicating a conformational nature of its epitope. It bound to a 5-helix bundle but not to N-heptad repeat coiled coils and a 6-helix bundle construct indicating contribution of both gp41 heptad repeats to its epitope and to a possible mechanism of neutralization. These results indicate that the R2 Env may contain unique exposed conserved epitopes that could contribute to its ability to elicit broadly cross-reactive antibodies in animals and humans; the newly identified antibodies may help in the development of novel vaccine immunogens and therapeutics. © 2007 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/157477
ISSN
2015 Impact Factor: 3.2
2015 SCImago Journal Rankings: 1.805
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChoudhry, Ven_US
dc.contributor.authorZhang, MYen_US
dc.contributor.authorSidorov, IAen_US
dc.contributor.authorLouis, JMen_US
dc.contributor.authorHarris, Ien_US
dc.contributor.authorDimitrov, ASen_US
dc.contributor.authorBouma, Pen_US
dc.contributor.authorCham, Fen_US
dc.contributor.authorChoudhary, Aen_US
dc.contributor.authorRybak, SMen_US
dc.contributor.authorFouts, Ten_US
dc.contributor.authorMontefiori, DCen_US
dc.contributor.authorBroder, CCen_US
dc.contributor.authorQuinnan Jr, GVen_US
dc.contributor.authorDimitrov, DSen_US
dc.date.accessioned2012-08-08T08:50:20Z-
dc.date.available2012-08-08T08:50:20Z-
dc.date.issued2007en_US
dc.identifier.citationVirology, 2007, v. 363 n. 1, p. 79-90en_US
dc.identifier.issn0042-6822en_US
dc.identifier.urihttp://hdl.handle.net/10722/157477-
dc.description.abstractElicitation of broadly cross-reactive neutralizing antibodies (bcnAbs) in HIV infections is rare. To test the hypothesis that such antibodies could be elicited by HIV envelope glycoproteins (Envs) with unusual immunogenic properties and to identify novel bcnAbs, we used a soluble Env ectodomain (gp140) from a donor (R2) with high level of bcnAbs as an antigen for panning of an immune phage-displayed antibody library. The panning with the R2 Env resulted in significantly higher number of cross-reactive antibody clones than by using Envs from two other isolates (89.6 and IIIB). Two of the identified human monoclonal antibodies (hmAbs), m22 and m24, had sequences, neutralizing and binding activities similar or identical to those of the gp120-specific bcnAbs m18 and m14. The use of the R2 Env but not other Envs for panning resulted in the identification of a novel gp41-specific hmAb, m46. For several of the tested HIV-1 primary isolates its potency on molar basis was comparable to that of T20. It inhibited entry of primary isolates from different clades with an increased activity for cell lines with low CCR5 surface concentrations. The m46 neutralizing activity against a panel of clade C isolates was significantly higher in an assay based on peripheral blood mononuclear cells (4 out of 5 isolates were neutralized with an IC50 in the range from 1.5 to 25 μg/ml) than in an assay based on a cell line with relatively high concentration of cell-surface-associated CCR5. In contrast to 2F5 and Z13, this antibody did not bind to denatured gp140 and gp41-derived peptides indicating a conformational nature of its epitope. It bound to a 5-helix bundle but not to N-heptad repeat coiled coils and a 6-helix bundle construct indicating contribution of both gp41 heptad repeats to its epitope and to a possible mechanism of neutralization. These results indicate that the R2 Env may contain unique exposed conserved epitopes that could contribute to its ability to elicit broadly cross-reactive antibodies in animals and humans; the newly identified antibodies may help in the development of novel vaccine immunogens and therapeutics. © 2007 Elsevier Inc. All rights reserved.en_US
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yviroen_US
dc.relation.ispartofVirologyen_US
dc.subject.meshAntibodies, Monoclonal - Immunology - Isolation & Purificationen_US
dc.subject.meshBinding, Competitiveen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCross Reactions - Immunologyen_US
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_US
dc.subject.meshGene Products, Env - Immunologyen_US
dc.subject.meshHiv Antibodies - Immunologyen_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 - Immunologyen_US
dc.subject.meshNeutralization Testsen_US
dc.subject.meshPeptide Libraryen_US
dc.subject.meshEnv Gene Products, Human Immunodeficiency Virusen_US
dc.titleCross-reactive HIV-1 neutralizing monoclonal antibodies selected by screening of an immune human phage library against an envelope glycoprotein (gp140) isolated from a patient (R2) with broadly HIV-1 neutralizing antibodiesen_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.virol.2007.01.015en_US
dc.identifier.pmid17306322-
dc.identifier.scopuseid_2-s2.0-34247559067en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34247559067&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume363en_US
dc.identifier.issue1en_US
dc.identifier.spage79en_US
dc.identifier.epage90en_US
dc.identifier.isiWOS:000246936000009-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChoudhry, V=8530897500en_US
dc.identifier.scopusauthoridZhang, MY=35316639300en_US
dc.identifier.scopusauthoridSidorov, IA=7005186545en_US
dc.identifier.scopusauthoridLouis, JM=7202523747en_US
dc.identifier.scopusauthoridHarris, I=14070327900en_US
dc.identifier.scopusauthoridDimitrov, AS=7101600999en_US
dc.identifier.scopusauthoridBouma, P=7003730370en_US
dc.identifier.scopusauthoridCham, F=6507851729en_US
dc.identifier.scopusauthoridChoudhary, A=8743351100en_US
dc.identifier.scopusauthoridRybak, SM=35453517100en_US
dc.identifier.scopusauthoridFouts, T=6603607043en_US
dc.identifier.scopusauthoridMontefiori, DC=7005651585en_US
dc.identifier.scopusauthoridBroder, CC=7004376461en_US
dc.identifier.scopusauthoridQuinnan Jr, GV=7006729933en_US
dc.identifier.scopusauthoridDimitrov, DS=7202564539en_US

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