Transient rapamycin treatment avoids unwanted host immune responses toward AAV-delivered anti-HIV antibodies.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41057323.
- Also identified by DOI 10.1038/s41467-025-63970-6 and PMC identifier 12504686.
- Licence recorded as CC BY-NC-ND.
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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.
Medical subject headings
- Dependovirus
- Sirolimus
- HIV Infections
- HIV Antibodies
- Antibodies, Neutralizing