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VIRAEMIA SUPPRESSED IN HIV-1-INFECTED HUMANS BY BROADLY NEUTRALIZING ANTIBODY 3BNC117
| Thursday, 9th of April 2015 |
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VIRAEMIA SUPPRESSED IN HIV-1-INFECTED HUMANS BY BROADLY NEUTRALIZING ANTIBODY 3BNC117
- Marina Caskey,
- Florian Klein,
- Julio C. C. Lorenzi,
- Michael S. Seaman,
- Anthony P. West Jr,
- Noreen Buckley,
- Gisela Kremer,
- Lilian Nogueira,
- Malte Braunschweig,
- Johannes F. Scheid,
- Joshua A. Horwitz,
- Irina Shimeliovich,
- Sivan Ben-Avraham,
- Maggi Witmer-Pack,
- Martin Platten,
- Clara Lehmann,
- Leah A. Burke,
- Thomas Hawthorne,
- Robert J. Gorelick,
- Bruce D. Walker,
- Tibor Keler,
- Roy M. Gulick,
- Gerd Fätkenheuer,
- Sarah J. Schlesinger
- & Michel C. Nussenzweig
Abstract below; full text is available to journal subscribers.
HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned1, 2, 3. 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 evaluated6, 7, 8, 9, 10. Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody11, 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.
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| www.measlesinitiative.org www.technet21.org www.polioeradication.org www.globalhealthlearning.org www.who.int/bulletin allianceformalariaprevention.com www.malariaworld.org http://www.panafrican-med-journal.com/ |