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

Sebastian P. Fuchs, Paula G. Mondragon, Rachel Zabizhin, Shallu Tomer, Li Wang, Ethan Cook, Dawn M. Dudley, Kimberly L. Weisgrau, Jessica Furlott, Jennifer Coonen, Eric Alexander, Jun Xie, Guangping Gao, James M. Termini, Jose M. Martinez-Navio, Anjie Zhen () and Ronald C. Desrosiers ()
Additional contact information
Sebastian P. Fuchs: University of Miami
Paula G. Mondragon: University of Miami
Rachel Zabizhin: University of Miami
Shallu Tomer: University of California—Los Angeles
Li Wang: University of California—Los Angeles
Ethan Cook: University of California—Los Angeles
Dawn M. Dudley: University of Wisconsin
Kimberly L. Weisgrau: University of Wisconsin
Jessica Furlott: University of Wisconsin
Jennifer Coonen: University of Wisconsin
Eric Alexander: University of Wisconsin
Jun Xie: UMass Chan Medical School
Guangping Gao: UMass Chan Medical School
James M. Termini: University of Miami
Jose M. Martinez-Navio: University of Miami
Anjie Zhen: University of California—Los Angeles
Ronald C. Desrosiers: University of Miami

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-63970-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63970-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-63970-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().