Show simple item record Zhang, MY Borges, AR Ptak, RG Wang, Y Dimitrov, AS Alam, SM Wieczorek, L Bouma, P Fouts, T Jiang, S Polonis, VR Haynes, BF Quinnan, GV Montefiori, DC Dimitrov, DS
dc.coverage.spatial United States 2011-06-21T17:22:00Z 2010-05
dc.identifier 11416
dc.identifier.citation MAbs, 2010, 2 (3), pp. 266 - 274
dc.description.abstract Several 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 IgG(1) 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.
dc.format.extent 266 - 274
dc.language eng
dc.language.iso en_US en_US
dc.relation.ispartof MAbs
dc.subject Anti-HIV Agents
dc.subject Antibodies, Neutralizing
dc.subject Antibody Specificity
dc.subject Antigens, CD4
dc.subject Cell Line
dc.subject Dose-Response Relationship, Immunologic
dc.subject Epitopes
dc.subject HIV Antibodies
dc.subject HIV Envelope Protein gp120
dc.subject HIV Infections
dc.subject HIV-1
dc.subject Humans
dc.subject Peptide Fragments
dc.subject Single-Chain Antibodies
dc.title Potent and broad neutralizing activity of a single chain antibody fragment against cell-free and cell-associated HIV-1.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US 2010-6-may en_US
duke.description.endpage 274 en_US
duke.description.issue 3 en_US
duke.description.startpage 266 en_US
duke.description.volume 2 en_US
dc.relation.journal Mabs en_US
pubs.issue 3
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Institutes and Provost's Academic Units
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers/Global Health Institute
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Immunology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Duke Human Vaccine Institute
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery/Surgery, Surgical Sciences Section for AIDS Research & Development
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Human Vaccine Institute
pubs.publication-status Published
pubs.volume 2
dc.identifier.eissn 1942-0870

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