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

PloS One
Davide CortiAntonio Lanzavecchia

Abstract

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. 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...Continue Reading

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Citations

Jul 11, 2013·Clinical & Developmental Immunology·Andrew HiattKevin J Whaley
Jan 30, 2014·Viruses·Lili Yang, Pin Wang
Mar 13, 2014·The Journal of Clinical Investigation·Mattia BonsignoriBarton F Haynes
Mar 29, 2014·Current Opinion in HIV and AIDS·Quentin J Sattentau
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Methods Mentioned

BETA
ELISA
FCS
Assay
fluorescence microscopy
ELISAs
immunoprecipitation

Software Mentioned

Pepscan

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