| Literature DB >> 30850342 |
José M Martinez-Navio1, Sebastian P Fuchs1, Shara N Pantry1, William A Lauer1, Natasha N Duggan1, Brandon F Keele2, Eva G Rakasz3, Guangping Gao4, Jeffrey D Lifson2, Ronald C Desrosiers5.
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.Entities:
Keywords: AAV vector; HIV broadly neutralizing antibodies; SHIV infection; adeno-associated virus; anti-drug antibodies; functional cure; gene therapy; immunotherapy; rhesus macaques; viral reservoir
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Year: 2019 PMID： 30850342 PMCID： PMC6457122 DOI： 10.1016/j.immuni.2019.02.005
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745