2. Academic Validation
  3. Transient rapamycin treatment avoids unwanted host immune responses toward AAV-delivered anti-HIV antibodies

Transient rapamycin treatment avoids unwanted host immune responses toward AAV-delivered anti-HIV antibodies

  • Nat Commun. 2025 Oct 7;16(1):8906. doi: 10.1038/s41467-025-63970-6.
Sebastian P Fuchs 1,  Paula G Mondragon 1,  Rachel Zabizhin 1,  Shallu Tomer 2,  Li Wang 2,  Ethan Cook 2,  Dawn M Dudley 3,  Kimberly L Weisgrau 3,  Jessica Furlott 3,  Jennifer Coonen 3,  Eric Alexander 3,  Jun Xie 4,  Guangping Gao 4,  James M Termini 1,  Jose M Martinez-Navio 1,  Anjie Zhen 5,  Ronald C Desrosiers 6
Affiliations

Affiliations

  • 1 Department of Pathology and Laboratory Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA.
  • 2 Department of Hematology/Oncology, University of California-Los Angeles, Los Angeles, CA, USA.
  • 3 Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, USA.
  • 4 Department of Genetics & Cellular Medicine, Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA.
  • 5 Department of Hematology/Oncology, University of California-Los Angeles, Los Angeles, CA, USA. AZhen@mednet.ucla.edu.
  • 6 Department of Pathology and Laboratory Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA. r.desrosiers@med.miami.edu.
PMID: 41057323 DOI: 10.1038/s41467-025-63970-6
Abstract

Long-term delivery of broadly neutralizing antibodies (bnAbs) using adeno-associated virus (AAV) vector is a promising approach for both the prevention and treatment of HIV Infection. However, host anti-drug antibody (ADA) responses severely limit the continuous delivery of these anti-HIV bnAbs and have been the most important obstacle for development of this approach for widespread human use. Transient treatment with the immunomodulatory agent rapamycin (sirolimus) allows for continuous long-term delivery of the anti-HIV bnAb 3BNC117 in immunocompetent mice in the absence of detectable ADAs. Use of the agent in monkeys results in 12 of 15 successful deliveries of the bnAbs 3BNC117, 10-1074, and PGT145 following drug cessation across all Animals. The results of this 5-monkey trial lend strong support to continuing studies in SHIV-infected monkeys and use of this approach in humans for potential worldwide use.

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