Details

Autor(en) / Beteiligte

• Joyce, M. Gordon
• Georgiev, Ivelin S.
• Yang, Yongping
• Druz, Aliaksandr
• Geng, Hui
• Chuang, Gwo-Yu
• Kwon, Young Do
• Pancera, Marie
• Rawi, Reda
• Sastry, Mallika
• Stewart-Jones, Guillaume B.E.
• Zheng, Angela
• Zhou, Tongqing
• Choe, Misook
• Van Galen, Joseph G.
• Chen, Rita E.
• Lees, Christopher R.
• Narpala, Sandeep
• Chambers, Michael
• Tsybovsky, Yaroslav
• Baxa, Ulrich
• McDermott, Adrian B.
• Mascola, John R.
• Kwong, Peter D.

Titel

Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains

Ist Teil von

• Cell reports (Cambridge), 2017-12, Vol.21 (10), p.2992-3002

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• The elicitation of autologous neutralizing responses by immunization with HIV-1 envelope (Env) trimers conformationally stabilized in a prefusion closed state has generated considerable interest in the HIV-1 vaccine field. However, soluble prefusion closed Env trimers have been produced from only a handful of HIV-1 strains, limiting their utility as vaccine antigens and B cell probes. Here, we report the engineering from 81 HIV-1 strains of soluble, fully cleaved, prefusion Env trimers with appropriate antigenicity. We used a 96-well expression-screening format to assess the ability of artificial disulfides and Ile559Pro substitution (DS-SOSIP) to produce soluble cleaved-Env trimers; from 180 Env strains, 20 yielded prefusion closed trimers. We also created chimeras, by utilizing structure-based design to incorporate select regions from the well-behaved BG505 strain; from 180 Env strains, 78 DS-SOSIP-stabilized chimeras, including 61 additional strains, yielded prefusion closed trimers. Structure-based design thus enables the production of prefusion closed HIV-1-Env trimers from dozens of diverse strains. [Display omitted] •Identified 20 strains of HIV-1 compatible with prefusion DS-SOSIP stabilization•Utilized a chimeric strategy to increase the number of stabilized strains•Produced prefusion closed DS-SOSIP-stabilized Env chimeras from 81 strains•Stabilized Env chimeras should have utility as HIV-1 immunogens and B cell probes Joyce et al. use a structure-based chimeric strategy to produce prefusion closed Env trimers from 81 strains of HIV-1 encompassing all major clades. These soluble Env trimers should have utility as B cell probes and HIV-1 immunogens, thereby enabling both antibody identification and vaccine development.