Scholarlink

<p>Broadly neutralizing antibodies (bnAbs) are promising agents for HIV-1 treatment and prevention. However, the genetic barriers and mutational pathways to viral resistance, which can limit therapeutic antibody utility, remain poorly defined. Here we developed a medium-to-high throughput approach to determine the mutations that confer resistance to neutralization by the bnAbs 3BNC117 and 10-1074 currently in clinical development. We performed 7,776 parallel selection experiments to identify bnAb resistance mutations in 15 primary isolates that span global HIV-1 genetic diversity. There was substantial variability among HIV-1 isolates in the identity of mutations that conferred bnAb resistance. For 12 of 15 HIV-1 isolates, single amino acid changes could increase bnAb IC<sub>80</sub> to &gt;10 μg ml<sup>−1</sup>. Some 3BNC117 resistance mutations conferred resistance to additional bnAbs targeting the same or different epitopes, and unconventional escape mechanisms were occasionally encountered. These data provide a rationale for selecting bnAb combinations that are most likely to achieve treatment success.</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

Diverse paths to broadly neutralizing antibody escape among HIV-1 strains

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月11日

查看全文
  • Alex C. Stabell,
  • Songhee Lee,
  • Debby J. Park,
  • Christy L. Lavine,
  • Sebastian Mejia Espinosa,
  • Viren A. Baharani,
  • Rachel Patejak,
  • Michel C. Nussenzweig,
  • Marina Caskey,
  • Michael S. Seaman,
  • Paul D. Bieniasz,
  • Theodora Hatziioannou

摘要

Broadly neutralizing antibodies (bnAbs) are promising agents for HIV-1 treatment and prevention. However, the genetic barriers and mutational pathways to viral resistance, which can limit therapeutic antibody utility, remain poorly defined. Here we developed a medium-to-high throughput approach to determine the mutations that confer resistance to neutralization by the bnAbs 3BNC117 and 10-1074 currently in clinical development. We performed 7,776 parallel selection experiments to identify bnAb resistance mutations in 15 primary isolates that span global HIV-1 genetic diversity. There was substantial variability among HIV-1 isolates in the identity of mutations that conferred bnAb resistance. For 12 of 15 HIV-1 isolates, single amino acid changes could increase bnAb IC80 to >10 μg ml−1. Some 3BNC117 resistance mutations conferred resistance to additional bnAbs targeting the same or different epitopes, and unconventional escape mechanisms were occasionally encountered. These data provide a rationale for selecting bnAb combinations that are most likely to achieve treatment success.