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Article: Potent and broad neutralizing activity of a single chain antibody fragment against cell-free and cell-associated HIV-1

TitlePotent and broad neutralizing activity of a single chain antibody fragment against cell-free and cell-associated HIV-1
Authors
KeywordsAIDS
Antibodies
HIV
Microbicides
scFv
Therapeutics
Vaccines
Issue Date2010
PublisherLandes Bioscience. The Journal's web site is located at http://www.landesbioscience.com/journals/mabs/
Citation
mAbs, 2010, v. 2 n. 3, p. 266-274 How to Cite?
AbstractSeveral human monoclonal antibodies (hmAbs) exhibit relatively potent and broad neutralizing activity against HIV-1, but there has not been much success in using them as potential therapeutics. We have previously hypothesized and demonstrated that small engineered antibodies can target highly conserved epitopes that are not accessible by full-size antibodies. However, their potency has not been comparatively evaluated with known HIV-1-neutralizing hmAbs against large panels of primary isolates. We report here the inhibitory activity of an engineered single chain antibody fragment (scFv), m9, against several panels of primary HIV-1 isolates from group M (clades A-G) using cell-free and cell-associated virus in cell line-based assays. M9 was much more potent than scFv 17b, and more potent than or comparable to the best-characterized broadly neutralizing hmAbs IgG1 b12, 2G12, 2F5 and 4e10. It also inhibited cell-to-cell transmission of HIV-1 with higher potency than enfuvirtide (t-20, Fuzeon). M9 competed with a sulfated CCR5 N-terminal peptide for binding to gp120-CD4 complex, suggesting an overlapping epitope with the coreceptor binding site. M9 did not react with phosphatidylserine (pS) and cardiolipin (CL), nor did it react with a panel of autoantigens in an antinuclear autoantibody (ANA) assay. We further found that escape mutants resistant to m9 did not emerge in an immune selection assay. these results suggest that m9 is a novel anti-HIV-1 candidate with potential therapeutic or prophylactic properties, and its epitope is a new target for drug or vaccine development. © 2010 Landes Bioscience.
Persistent Identifierhttp://hdl.handle.net/10722/65508
ISSN
2015 Impact Factor: 4.161
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhang, MYen_HK
dc.contributor.authorBorges, ARen_HK
dc.contributor.authorPtak, RGen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorDimitrov, ASen_HK
dc.contributor.authorAlam, SMen_HK
dc.contributor.authorWieczorek, Len_HK
dc.contributor.authorBouma, Pen_HK
dc.contributor.authorFouts, Ten_HK
dc.contributor.authorJiang, Sen_HK
dc.contributor.authorPolonis, VRen_HK
dc.contributor.authorHaynes, BFen_HK
dc.contributor.authorQuinnan, GVen_HK
dc.contributor.authorMontefiori, DCen_HK
dc.contributor.authorDimitrov, DSen_HK
dc.date.accessioned2010-08-31T04:02:38Z-
dc.date.available2010-08-31T04:02:38Z-
dc.date.issued2010en_HK
dc.identifier.citationmAbs, 2010, v. 2 n. 3, p. 266-274en_HK
dc.identifier.issn1942-0862en_HK
dc.identifier.urihttp://hdl.handle.net/10722/65508-
dc.description.abstractSeveral human monoclonal antibodies (hmAbs) exhibit relatively potent and broad neutralizing activity against HIV-1, but there has not been much success in using them as potential therapeutics. We have previously hypothesized and demonstrated that small engineered antibodies can target highly conserved epitopes that are not accessible by full-size antibodies. However, their potency has not been comparatively evaluated with known HIV-1-neutralizing hmAbs against large panels of primary isolates. We report here the inhibitory activity of an engineered single chain antibody fragment (scFv), m9, against several panels of primary HIV-1 isolates from group M (clades A-G) using cell-free and cell-associated virus in cell line-based assays. M9 was much more potent than scFv 17b, and more potent than or comparable to the best-characterized broadly neutralizing hmAbs IgG1 b12, 2G12, 2F5 and 4e10. It also inhibited cell-to-cell transmission of HIV-1 with higher potency than enfuvirtide (t-20, Fuzeon). M9 competed with a sulfated CCR5 N-terminal peptide for binding to gp120-CD4 complex, suggesting an overlapping epitope with the coreceptor binding site. M9 did not react with phosphatidylserine (pS) and cardiolipin (CL), nor did it react with a panel of autoantigens in an antinuclear autoantibody (ANA) assay. We further found that escape mutants resistant to m9 did not emerge in an immune selection assay. these results suggest that m9 is a novel anti-HIV-1 candidate with potential therapeutic or prophylactic properties, and its epitope is a new target for drug or vaccine development. © 2010 Landes Bioscience.en_HK
dc.languageeng-
dc.publisherLandes Bioscience. The Journal's web site is located at http://www.landesbioscience.com/journals/mabs/en_HK
dc.relation.ispartofmAbsen_HK
dc.subjectAIDSen_HK
dc.subjectAntibodiesen_HK
dc.subjectHIVen_HK
dc.subjectMicrobicidesen_HK
dc.subjectscFven_HK
dc.subjectTherapeuticsen_HK
dc.subjectVaccinesen_HK
dc.titlePotent and broad neutralizing activity of a single chain antibody fragment against cell-free and cell-associated HIV-1en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1942-0862&volume=2&issue=3&spage=266&epage=274&date=2010&atitle=Potent+and+broad+neutralizing+activity+of+a+single+chain+antibody+fragment+against+cell-free+and+cell-associated+HIV-1-
dc.identifier.emailZhang, MY:zhangmy@hku.hken_HK
dc.identifier.authorityZhang, MY=rp01409en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.4161/mabs.2.3.11416en_HK
dc.identifier.pmid20305395-
dc.identifier.pmcidPMC2881253-
dc.identifier.scopuseid_2-s2.0-77953664634en_HK
dc.identifier.hkuros170376-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953664634&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume2en_HK
dc.identifier.issue3en_HK
dc.identifier.spage266en_HK
dc.identifier.epage274en_HK
dc.identifier.isiWOS:000281388200006-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZhang, MY=35316639300en_HK
dc.identifier.scopusauthoridBorges, AR=23979626400en_HK
dc.identifier.scopusauthoridPtak, RG=7004558299en_HK
dc.identifier.scopusauthoridWang, Y=9747395700en_HK
dc.identifier.scopusauthoridDimitrov, AS=7101600999en_HK
dc.identifier.scopusauthoridAlam, SM=7202098953en_HK
dc.identifier.scopusauthoridWieczorek, L=24073729000en_HK
dc.identifier.scopusauthoridBouma, P=7003730370en_HK
dc.identifier.scopusauthoridFouts, T=6603607043en_HK
dc.identifier.scopusauthoridJiang, S=7404453146en_HK
dc.identifier.scopusauthoridPolonis, VR=6603744791en_HK
dc.identifier.scopusauthoridHaynes, BF=26430746300en_HK
dc.identifier.scopusauthoridQuinnan, GV=7006729933en_HK
dc.identifier.scopusauthoridMontefiori, DC=7005651585en_HK
dc.identifier.scopusauthoridDimitrov, DS=7202564539en_HK

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