Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.

Corti, Davide

Langedijk, Johannes PM

Hinz, Andreas

Seaman, Michael S

Vanzetta, Fabrizia

Fernandez-Rodriguez, Blanca M

Silacci, Chiara

Pinna, Debora

Jarrossay, David

Balla-Jhagjhoorsingh, Sunita

Willems, Betty

Zekveld, Maria J

Dreja, Hanna

O'Sullivan, Eithne

Pade, Corinna

Orkin, Chloe

Jeffs, Simon A

Montefiori, David C

Davis, David

Weissenhorn, Winfried

McKnight, Aine

Heeney, Jonathan L

Sallusto, Federica

Sattentau, Quentin J

Weiss, Robin A

Lanzavecchia, Antonio

Unutmaz, Derya

United States

2011-06-21T17:31:27Z

2010-01-20

BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.

Version of Record

https://www.ncbi.nlm.nih.gov/pubmed/20098712

1932-6203

https://hdl.handle.net/10161/4523

eng

en_US

Public Library of Science (PLoS)

PLoS One

10.1371/journal.pone.0008805

Plos One

Amino Acid Sequence

Antibodies, Monoclonal

Antibodies, Neutralizing

Antigens, CD4

B-Lymphocytes

Binding Sites, Antibody

Epitopes

HIV Infections

HIV-1

Humans

Immunologic Memory

Molecular Sequence Data

Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.

Journal article

Montefiori, David C|0000-0003-0856-6319

2010-1-20

1

5

https://www.ncbi.nlm.nih.gov/pubmed/20098712

e8805

1

Clinical Science Departments

Duke

Duke Human Vaccine Institute

Institutes and Centers

School of Medicine

Surgery

Surgery, Surgical Sciences

Published online

5