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Adeno-Associated Virus Delivery of Anti-HIV Monoclonal Antibodies Can Drive Long-Term Virologic Suppression

  1. Author:
    Martinez-Navio, José M
    Fuchs, Sebastian P
    Pantry, Shara N
    Lauer, William A
    Duggan, Natasha N
    Keele, Brandon
    Rakasz, Eva G
    Gao, Guangping
    Lifson, Jeffrey
    Desrosiers, Ronald C

  2. Author Address

    Department of Pathology, Miller School of Medicine, University of Miami, Miami, Florida, USA., AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA., Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, USA., Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA., Department of Pathology, Miller School of Medicine, University of Miami, Miami, Florida, USA. Electronic address: r.desrosiers@med.miami.edu.,
    1. Year: 2019
    2. Date: Mar 19
    3. Epub Date: 2019 02 20
  2. Journal: Immunity
    1. 50
    2. 3
    3. Pages: 567-+
  4. Type of Article: Article
  5. ISSN: 1074-7613
  1. Abstract:

    Long-term delivery of anti-HIV monoclonal antibodies (mAbs) using adeno-associated virus (AAV) vectors holds promise for the prevention and treatment of HIV infection. We describe a therapy trial in which four rhesus monkeys were infected with SHIV-AD8 for 86 weeks before receiving the AAV-encoded mAbs 3BNC117, 10-1074, and 10E8. Although anti-drug antibody (ADA) responses restricted mAb delivery, one monkey successfully maintained 50-150 µg/mL of 3BNC117 and 10-1074 for over 2 years. Delivery of these two mAbs to this monkey resulted in an abrupt decline in plasma viremia, which remained undetectable for 38 successive measurements over 3 years. We generated two more examples of virologic suppression using AAV delivery of a cocktail of four mAbs in a 12-monkey study. Our results provide proof of concept for AAV-delivered mAbs to produce a "functional cure." However, they also serve as a warning that ADAs may be a problem for practical application of this approach in humans. Copyright © 2019. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.immuni.2019.02.005
  3. PMID: 30850342
  4. PMCID: PMC6457122
  5. View record in Web of Science®
  6. WOS: 000461660500009
  7. PII : S1074-7613(19)30071-8

Library Notes

  1. Fiscal Year: FY2018-2019
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