Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains.
Publication/Presentation Date
12-5-2017
Abstract
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.
Volume
21
Issue
10
First Page
2992
Last Page
3002
ISSN
2211-1247
Published In/Presented At
Joyce, M. G., Georgiev, I. S., Yang, Y., Druz, A., Geng, H., Chuang, G. Y., Kwon, Y. D., Pancera, M., Rawi, R., Sastry, M., Stewart-Jones, G. B. E., Zheng, A., Zhou, T., Choe, M., Van Galen, J. G., Chen, R. E., Lees, C. R., Narpala, S., Chambers, M., Tsybovsky, Y., … Kwong, P. D. (2017). Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains. Cell reports, 21(10), 2992–3002. https://doi.org/10.1016/j.celrep.2017.11.016
Disciplines
Medicine and Health Sciences
PubMedID
29212041
Department(s)
Department of Medicine
Document Type
Article