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

Immunity. 2019 Mar 19;50(3):567-575.e5. doi: 10.1016/j.immuni.2019.02.005. Epub 2019 Mar 5.


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.

Keywords: AAV vector; HIV broadly neutralizing antibodies; SHIV infection; adeno-associated virus; anti-drug antibodies; functional cure; gene therapy; immunotherapy; rhesus macaques; viral reservoir.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing / immunology
  • Broadly Neutralizing Antibodies
  • Cell Line
  • Dependovirus / immunology*
  • HEK293 Cells
  • HIV Antibodies / immunology
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Macaca mulatta
  • Viremia / immunology


  • 3BNC117 antibody
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • HIV Antibodies