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 Chang; Steven W. King; Anita Kavlie; Thomas N. Denny; Kwan Ki Hwang; Pojen P. Chen; Philip E. Thorpe; David C. Montefiori; Barton F. Haynes

doi:10.1084/jem.20091281

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

Pharmacology

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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 language	English (US)
Pages (from-to)	763-776
Number of pages	14
Journal	Journal of Experimental Medicine
Volume	207
Issue number	4
DOIs	https://doi.org/10.1084/jem.20091281
State	Published - Apr 12 2010

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Medicine(all)

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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

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 2010, 'Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce β-chemokines', Journal of Experimental Medicine, vol. 207, no. 4, pp. 763-776. https://doi.org/10.1084/jem.20091281

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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.",

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AU - Plonk, M. Kelly

AU - Kozink, Daniel M.

AU - Drinker, Mark S.

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AU - Tomaras, Georgia D.

AU - Giles, Ian P.

AU - Kappes, John C.

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AU - Soares, Melina

AU - Barbero, Gustavo

AU - Forthal, Donald N.

AU - Landucci, Gary

AU - Chang, Connie

AU - King, Steven W.

AU - Kavlie, Anita

AU - Denny, Thomas N.

AU - Hwang, Kwan Ki

AU - Chen, Pojen P.

AU - Thorpe, Philip E.

AU - Montefiori, David C.

AU - Haynes, Barton F.

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

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