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

• Published in: Cell reports (Cambridge) Vol. 21; no. 10; pp. 2992 - 3002
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.12.2017; Elsevier
• Subjects: AIDS Vaccines - immunology; conformational stabilization; env Gene Products, Human Immunodeficiency Virus - immunology; env Gene Products, Human Immunodeficiency Virus - metabolism; envelope trimer; Enzyme-Linked Immunosorbent Assay; HIV-1 - immunology; HIV-1 - metabolism; HIV-1 vaccine; Microscopy, Electron; prefusion closed trimer; structure-based design; prefusion closed trimer; HIV-1 vaccine; envelope trimer; conformational stabilization; structure-based design
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.11.016

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.