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

M. Anthony Moody, Hua Xin Liao, S. Munir Alam, Richard M. Scearce, M. Kelly Plonk, Daniel M. Kozink, Mark S. Drinker, Ruijun Zhang, Shi Mao Xia, Laura L. Sutherland, Georgia D. Tomaras, Ian P. Giles, John C. Kappes, Christina Ochsenbauer-Jambor, Tara G. Edmonds, Melina Soares, Gustavo Barbero, Donald N. Forthal, Gary Landucci, Connie ChangSteven W. King, Anita Kavlie, Thomas N. Denny, Kwan Ki Hwang, Pojen P. Chen, Philip E. Thorpe, David C. Montefiori, Barton F. Haynes

Research output: Contribution to journalArticle

43 Scopus citations

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 ∼10 μg/ml. Anti-phospholipid mAbs inhibited PBMC HIV-1 infection in vitro by mechanisms involving binding to monocytes and triggering the release of MIP-1α and MIP-1β. The release of these β-chemokines explains both the specificity for R5 HIV-1 and the activity of these mAbs in PBMC cultures containing both primary lymphocytes and monocytes.

Original languageEnglish (US)
Pages (from-to)763-776
Number of pages14
JournalJournal of Experimental Medicine
Volume207
Issue number4
DOIs
StatePublished - Apr 12 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Moody, M. A., Liao, H. X., Alam, S. M., Scearce, R. M., Plonk, M. K., Kozink, D. M., Drinker, M. S., Zhang, R., Xia, S. M., Sutherland, L. L., Tomaras, G. D., Giles, I. P., Kappes, J. C., Ochsenbauer-Jambor, C., Edmonds, T. G., Soares, M., Barbero, G., Forthal, D. N., Landucci, G., ... Haynes, B. F. (2010). Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce β-chemokines. Journal of Experimental Medicine, 207(4), 763-776. https://doi.org/10.1084/jem.20091281