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

dc.contributor.author

Zhang, MY

dc.contributor.author

Borges, AR

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Ptak, RG

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Wang, Y

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Dimitrov, AS

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Alam, SM

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Wieczorek, L

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Bouma, P

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Fouts, T

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Jiang, S

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Polonis, VR

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Haynes, BF

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Quinnan, GV

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Montefiori, DC

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Dimitrov, DS

dc.coverage.spatial

United States

dc.date.accessioned

2011-06-21T17:22:00Z

dc.date.issued

2010-05

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.description.version

Version of Record

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/20305395

dc.identifier

11416

dc.identifier.eissn

1942-0870

dc.identifier.uri

https://hdl.handle.net/10161/3966

dc.language

eng

dc.language.iso

en_US

dc.publisher

Informa UK Limited

dc.relation.ispartof

MAbs

dc.relation.journal

Mabs

dc.subject

Anti-HIV Agents

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Antibodies, Neutralizing

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Antibody Specificity

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Antigens, CD4

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Cell Line

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Dose-Response Relationship, Immunologic

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Epitopes

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HIV Antibodies

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HIV Envelope Protein gp120

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HIV Infections

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HIV-1

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Humans

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Peptide Fragments

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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
dc.type

Journal article

duke.contributor.orcid

Montefiori, DC|0000-0003-0856-6319

duke.date.pubdate

2010-6-may

duke.description.issue

3

duke.description.volume

2

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/20305395

pubs.begin-page

266

pubs.end-page

274

pubs.issue

3

pubs.organisational-group

Basic Science Departments

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Clinical Science Departments

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Duke

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Duke Cancer Institute

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Duke Human Vaccine Institute

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Global Health Institute

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Immunology

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Institutes and Centers

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Institutes and Provost's Academic Units

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Medicine

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Medicine, Duke Human Vaccine Institute

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Pathology

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School of Medicine

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Surgery

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Surgery, Surgical Sciences Section for AIDS Research & Development

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University Institutes and Centers

pubs.publication-status

Published

pubs.volume

2

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