title: HIV therapy by a combination of broadly neutralizing antibodies in humanized mice.
abstract: Human antibodies to human immunodeficiency virus-1 (HIV-1) can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice. Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy, the longer half-life of antibodies led to control of viraemia for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in humanized mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Florian
authors.initials: F
authors.lastname: Klein
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Ariel
authors.initials: A
authors.lastname: Halper-Stromberg
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Horwitz
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University; New York, New York 10065; United States.|Medizinische Fakultät, Westfälische Wilhelms-Universität Münster; D-48149 Münster; Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Gruell
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University; New York, New York 10065; United States.|Charite Universitätsmedizin; D-10117 Berlin; Germany.
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Scheid
authors.affiliation: Laboratory of Molecular Genetics and Immunology, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Bournazos
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Hugo
authors.initials: H
authors.lastname: Mouquet
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University; New York, New York 10065; United States.|Department of Microbiology and Immunology, Sophie Davis School of Biomedical Education, The City College of New York; New York, New York 10031; United States.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Spatz
authors.affiliation: Division of Biology, California Institute of Technology; Pasadena, CA 91125; United States.
authors.forename: Ron
authors.initials: R
authors.lastname: Diskin
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Alexander
authors.initials: A
authors.lastname: Abadir
authors.affiliation: Aaron Diamond AIDS Research Center, Laboratory of Retrovirology, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Trinity
authors.initials: T
authors.lastname: Zang
authors.affiliation: Laboratory of Virology and Infectious Diseases, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Marcus
authors.initials: M
authors.lastname: Dorner
authors.affiliation: Laboratory of Virology and Infectious Diseases, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Eva
authors.initials: E
authors.lastname: Billerbeck
authors.affiliation: Laboratory of Virology and Infectious Diseases, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Rachael N
authors.initials: RN
authors.lastname: Labitt
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University; New York, New York 10065; United States.|Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden; D-01307 Dresden; Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gaebler
authors.affiliation: Division of Biology, California Institute of Technology; Pasadena, CA 91125; United States.
authors.forename: Paola
authors.initials: P
authors.lastname: Marcovecchio
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Reha-Baris
authors.initials: RB
authors.lastname: Incesu
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Eisenreich
authors.affiliation: Aaron Diamond AIDS Research Center, Laboratory of Retrovirology, The Rockefeller University; New York, New York 10065; United States.|Howard Hughes Medical Institute.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bieniasz
authors.affiliation: Beth Israel Deaconess Med. Ctr.; Boston, MA 02215; United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: Division of Biology, California Institute of Technology; Pasadena, CA 91125; United States.|Howard Hughes Medical Institute.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
authors.affiliation: Laboratory of Molecular Genetics and Immunology, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Ravetch
authors.affiliation: Laboratory of Virology and Infectious Diseases, The Rockefeller University; New York, New York 10065; United States.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploss
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University; New York, New York 10065; United States.|Howard Hughes Medical Institute.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000627:therapeutic use*; D000918:Antibody Specificity / Q000276:immunology; D004195:Disease Models, Animal; D015483:HIV Antibodies / Q000276:immunology* / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development / Q000276:immunology / Q000302:isolation & purification; D006207:Half-Life; D006801:Humans; D007116:Immunization, Passive; D051379:Mice; D016688:Mice, Inbred NOD; D013997:Time Factors; D019562:Viral Load / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies