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HIV therapy by a combination of broadly neutralizing antibodies in humanized mice

机译:通过在人源化小鼠中广泛中和抗体的组合进行HIV治疗

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针对“人免疫缺陷病毒-1”(HIV-1)的广谱中和rn抗体形成速度慢,仅见于少数患者,但它们能rn防止感染,因此对HIV疗法的设计有很大重要rn性。以前的研究工作表明,该病毒能很快形成rn对这些抗体的抵抗力;不过现在已经有了更强rn效的抗体。因此,Michel Nussenzwe。Mg及其同rn事对抗体疗法在“人化”小鼠身上的治疗潜力rn重新进行了研究。他们发现,用广谱中和抗体rn的组合进行的被动免疫疗法能有效控制HIV-1rn感染。他们提出,现在是重新审视单克隆抗体rn作为HIV-1感染者的治疗药物的时候了。%Human antibodies to human immunodeficiency virus-I (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-I antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HI V-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-I-infected individuals.
机译:针对“人免疫缺陷病毒-1”(HIV-1)的广谱中和rn抗体形成速度慢,仅见于少数患者,但它们能rn防止感染,因此对HIV疗法的设计有很大重要rn性。以前的研究工作表明,该病毒能很快形成rn对这些抗体的抵抗力;不过现在已经有了更强rn效的抗体。因此,Michel Nussenzwe。Mg及其同rn事对抗体疗法在“人化”小鼠身上的治疗潜力rn重新进行了研究。他们发现,用广谱中和抗体rn的组合进行的被动免疫疗法能有效控制HIV-1rn感染。他们提出,现在是重新审视单克隆抗体rn作为HIV-1感染者的治疗药物的时候了。%Human antibodies to human immunodeficiency virus-I (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-I antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HI V-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-I-infected individuals.

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  • 来源
    《Nature》 |2012年第7427期|118-122a4|共6页
  • 作者单位

    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA;

    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA;

    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA;

    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA,Medizinische Fakultat, Westfalische Wilhelms-Universitat Munster, D-48149 Munster, Germany.;

    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA,ChariteUniversitatsmedizin,D-10117 Berlin, Germany;

    Laboratory of MolecularGenetics and Immunology, The Rockefeller University, New York, New York 10065, USA;

    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA;

    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA,epartment of Microbiology and Immunology, Sophie Davis School of Biomedical Education, The City College of New York, New York, New York 10031, USA;

    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA;

    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA;

    Aaron Diamond AIDS Research Center, Laboratory of Retrovirology, The Rockefeller University, New York, New York 10065, USA;

    laboratory of Virology and infectious Diseases. The Rockefeller University, New York, New York 10065, USA;

    laboratory of Virology and infectious Diseases. The Rockefeller University, New York, New York 10065, USA;

    laboratory of Virology and infectious Diseases. The Rockefeller University, New York, New York 10065, USA;

    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA,Faculty of Medicine Carl Gustav Carus, Technische Universitat Dresden, D-01307 Dresden, Germany;

    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA;

    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA;

    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA;

    Aaron Diamond AIDS Research Center, Laboratory of Retrovirology, The Rockefeller University, New York, New York 10065, USA,Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA;

    Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA;

    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA,Howard Hughes Medical Institute, California Institute of Technology Pasadena. California 91125, USA;

    Laboratory of MolecularGenetics and Immunology, The Rockefeller University, New York, New York 10065, USA;

    laboratory of Virology and infectious Diseases. The Rockefeller University, New York, New York 10065, USA;

    Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA,Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA;

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