title: Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo.
abstract: Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-1-infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection but also include acceleration of infected cell clearance. Consistent with these observations, we find that broadly neutralizing antibodies can target CD4(+) T cells infected with patient viruses and can decrease their in vivo half-lives by a mechanism that requires Fcγ receptor engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1-infected cells.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Ching-Lan
authors.initials: CL
authors.lastname: Lu
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Dariusz K
authors.initials: DK
authors.lastname: Murakowski
authors.affiliation: Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Bournazos
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Till
authors.initials: T
authors.lastname: Schoofs
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Debolina
authors.initials: D
authors.lastname: Sarkar
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Halper-Stromberg
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Horwitz
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Lilian
authors.initials: L
authors.lastname: Nogueira
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Jovana
authors.initials: J
authors.lastname: Golijanin
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Gazumyan
authors.affiliation: Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Ravetch
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Caskey
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. nussen@rockefeller.edu arupc@mit.edu.
authors.forename: Arup K
authors.initials: AK
authors.lastname: Chakraborty
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. Howard Hughes Medical Institute. nussen@rockefeller.edu arupc@mit.edu.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D000080908:Broadly Neutralizing Antibodies; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000628:therapy* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007116:Immunization, Passive; D007165:Immunosuppression Therapy; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D017452:Receptors, IgG / Q000276:immunology; D019562:Viral Load / Q000276:immunology*
chemical_list: C000599675:3BNC117 antibody; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000080908:Broadly Neutralizing Antibodies; D015483:HIV Antibodies; D018398:Homeodomain Proteins; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D017452:Receptors, IgG; C064658:RAG-1 protein