J Exp Med. 2010 Apr 12; 207(4):763-76.

PubMed ID: 20368576

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

Moody MA, Liao HX, Alam SM, Scearce RM, Plonk MK, Kozink DM, Drinker MS, Zhang R, Xia SM, Sutherland LL, Tomaras GD, Giles IP, Kappes JC, Ochsenbauer-Jambor C, Edmonds TG, Soares M, Barbero G, Forthal DN, Landucci G, Chang C, King SW, Kavlie A, Denny TN, Hwang KK, Chen PP, Thorpe PE, Montefiori DC, Haynes BF

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.