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Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117

Caskey, Marina ; Klein, Florian ; Lorenzi, Julio C C ; Seaman, Michael S ; West, Jr, Anthony P ; Buckley, Noreen ; Kremer, Gisela ; Nogueira, Lilian ; Braunschweig, Malte ; Scheid, Johannes F ; Horwitz, Joshua A ; Shimeliovich, Irina ; Ben-Avraham, Sivan ; Witmer-Pack, Maggi ; Platten, Martin ; Lehmann, Clara ; Burke, Leah A ; Hawthorne, Thomas ; Gorelick, Robert J ; Walker, Bruce D ; Keler, Tibor ; Gulick, Roy M ; Fätkenheuer, Gerd ; Schlesinger, Sarah J ; Nussenzweig, Michel C

Nature (London), 2015-06, Vol.522 (7557), p.487-491 [Periódico revisado por pares]

England: Nature Publishing Group

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Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117
Autor: Caskey, Marina ; Klein, Florian ; Lorenzi, Julio C C ; Seaman, Michael S ; West, Jr, Anthony P ; Buckley, Noreen ; Kremer, Gisela ; Nogueira, Lilian ; Braunschweig, Malte ; Scheid, Johannes F ; Horwitz, Joshua A ; Shimeliovich, Irina ; Ben-Avraham, Sivan ; Witmer-Pack, Maggi ; Platten, Martin ; Lehmann, Clara ; Burke, Leah A ; Hawthorne, Thomas ; Gorelick, Robert J ; Walker, Bruce D ; Keler, Tibor ; Gulick, Roy M ; Fätkenheuer, Gerd ; Schlesinger, Sarah J ; Nussenzweig, Michel C
Assuntos: Adult ; Amino Acid Sequence ; Antibodies ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - pharmacokinetics ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Neutralizing - administration & dosage ; Antibodies, Neutralizing - adverse effects ; Antibodies, Neutralizing - immunology ; Antibodies, Neutralizing - pharmacology ; Antibodies, Neutralizing - therapeutic use ; Antigens ; Binding Sites ; Case-Control Studies ; CD4 Antigens - metabolism ; Drug dosages ; Evolution, Molecular ; Female ; HIV ; HIV Antibodies - administration & dosage ; HIV Antibodies - adverse effects ; HIV Antibodies - immunology ; HIV Antibodies - pharmacology ; HIV Antibodies - therapeutic use ; HIV Envelope Protein gp120 - chemistry ; HIV Envelope Protein gp120 - immunology ; HIV infection ; HIV infections ; HIV Infections - immunology ; HIV Infections - therapy ; HIV Infections - virology ; HIV-1 - chemistry ; HIV-1 - drug effects ; HIV-1 - immunology ; Human immunodeficiency virus ; Humans ; Immune system ; Immunization, Passive - methods ; Immunoglobulins ; Immunotherapy ; Infections ; Male ; Middle Aged ; Molecular Sequence Data ; Physiological aspects ; Time Factors ; Viral antibodies ; Viral Load - drug effects ; Viral Load - immunology ; Viremia - immunology ; Viremia - therapy ; Viremia - virology ; Virus diseases ; Young Adult
É parte de: Nature (London), 2015-06, Vol.522 (7557), p.487-491
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Descrição: HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned. However, recently developed single-cell-based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies to HIV-1 (refs 4, 5). These antibodies can prevent infection and suppress viraemia in humanized mice and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated. Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody, in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics. A single 30 mg kg(-1) infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8-2.5 log10 and viraemia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that, as a single agent, 3BNC117 is safe and effective in reducing HIV-1 viraemia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy and cure.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117

England: Nature Publishing Group

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