Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月7日

查看全文
  • 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,
  • Ronald C. Desrosiers

摘要

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.