...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>MBio >Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles
【24h】

Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles

机译：通过第一代GP41稳定的HIV-1包膜三聚体和纳米颗粒诱导的中和抗体

获取原文
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

ABSTRACT The immunogenicity of gp41-stabilized HIV-1 BG505 envelope (Env) trimers and nanoparticles (NPs) was recently assessed in mice and rabbits. Here, we combined Env-specific B-cell sorting and repertoire sequencing to identify neutralizing antibodies (NAbs) from immunized animals. A panel of mouse NAbs was isolated from mice immunized with a 60-meric I3-01 NP presenting 20 stabilized trimers. Three mouse NAbs potently neutralized BG505.T332N by recognizing a glycan epitope centered in the C3/V4 region on BG505 Env, as revealed by electron microscopy (EM), X-ray crystallography, and epitope mapping. A set of rabbit NAbs was isolated from rabbits immunized with a soluble trimer and a 24-meric ferritin NP presenting 8 trimers. Neutralization assays against BG505.T332N variants confirmed that potent rabbit NAbs targeted previously described glycan holes on BG505 Env and accounted for a significant portion of the autologous NAb response in both the trimer and ferritin NP groups. Last, we examined NAb responses that were induced by non-BG505 Env immunogens. We determined a 3.4-?-resolution crystal structure for the clade C transmitted/founder (T/F) Du172.17 Env with a redesigned heptad repeat 1 (HR1) bend in gp41. This clade C Env, in a soluble trimer form and in a multivalent form with 8 trimers attached to ferritin NP, and the gp41-stabilized clade A Q482-d12 Env trimer elicited distinct NAb responses in rabbits, with notable differences in neutralization breadth. Although eliciting a broad NAb response remains a major challenge, our study provides valuable information on an HIV-1 vaccine design strategy that combines gp41 stabilization and NP display.
机译：摘要最近在小鼠和兔中评估了GP41稳定的HIV-1 BG505包膜（ENV）三种封装和纳米颗粒（NPS）的免疫原性。这里，我们将Env特异性B细胞分选和再胃肠测序组合以鉴定来自免疫动物的中和抗体（NAB）。从用60毫米I3-01 NP呈现20稳定的三聚体免疫的小鼠中分离小鼠Nabs。通过识别在BG505 Env的C3 / V4区中的聚糖表位，如电子显微镜（EM），X射线晶体学和表位测绘透露，三个小鼠Nabs通过识别为中心的聚糖表位，通过电子显微镜（EM），X射线晶体学和表位测绘。从用可溶性三聚体免疫的兔子和呈现8个三聚体免疫的兔子中分离了一组兔Nabs。对BG505.T332N变体的中和测定证实，靶向BG505 ENV上先前描述的甘油孔的有效的兔NAB，并且在三聚体和铁蛋白NP基团中占AutolOnol Nab反应的重要部分。最后，我们检查了非BG505 Env免疫原诱导的NAB反应。我们确定了用于CLADE C发送/创始人（T / F）DU172.17 ENV的3.4 - θ - 分辨率晶体结构，重新设计的eptad重复1（HR1）弯曲在GP41中。该思想CEV，以可溶性三聚体形式和以含有8个三聚体的多元形式，与铁蛋白NP附着的8分段，并且GP41稳定的液体Q482-D12 Env三聚体引发了兔子中的不同的Nab反应，具有显着的中和宽度差异。虽然诱因广泛的NAB反应仍然是一个重大挑战，但我们的研究提供了关于HIV-1疫苗设计策略的有价值的信息，这些策略结合了GP41稳定和NP显示。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号