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

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 str

SUBMITTER: Fuchs SP 

PROVIDER: S-EPMC12504686 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature