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

Joyce MG, Georgiev IS, Yang Y, Druz A, Geng H, Chuang GY, Kwon YD, Pancera M, Rawi R, Sastry M, Stewart-Jones GBE, Zheng A, Zhou T, Choe M, Van Galen JG, Chen RE, Lees CR, Narpala S, Chambers M, Tsybovsky Y, Baxa U, McDermott AB, Mascola JR, Kwong PD
Cell Rep. 2017 21 (10): 2992-3002

PMID: 29212041 · 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.

Published by Elsevier Inc.

MeSH Terms (5)

AIDS Vaccines env Gene Products, Human Immunodeficiency Virus Enzyme-Linked Immunosorbent Assay HIV-1 Microscopy, Electron

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