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J Exp Med. 2010 Apr 12;207(4):763-76. doi: 10.1084/jem.20091281. Epub 2010 Apr 5.

Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce beta-chemokines.

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1
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. moody007@mc.duke.edu

Abstract

Traditional antibody-mediated neutralization of HIV-1 infection is thought to result from the binding of antibodies to virions, thus preventing virus entry. However, antibodies that broadly neutralize HIV-1 are rare and are not induced by current vaccines. We report that four human anti-phospholipid monoclonal antibodies (mAbs) (PGN632, P1, IS4, and CL1) inhibit HIV-1 CCR5-tropic (R5) primary isolate infection of peripheral blood mononuclear cells (PBMCs) with 80% inhibitory concentrations of <0.02 to approximately 10 microg/ml. Anti-phospholipid mAbs inhibited PBMC HIV-1 infection in vitro by mechanisms involving binding to monocytes and triggering the release of MIP-1alpha and MIP-1beta. The release of these beta-chemokines explains both the specificity for R5 HIV-1 and the activity of these mAbs in PBMC cultures containing both primary lymphocytes and monocytes.

PMID:
20368576
PMCID:
PMC2856026
DOI:
10.1084/jem.20091281
[Indexed for MEDLINE]
Free PMC Article

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