Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains
M. Gordon Joyce,
Ivelin S. Georgiev,
Yongping Yang,
Aliaksandr Druz,
Hui Geng,
Gwo-Yu Chuang,
Young Do Kwon,
Marie Pancera,
Reda Rawi,
Mallika Sastry,
Guillaume B.E. Stewart-Jones,
Angela Zheng,
Tongqing Zhou,
Misook Choe,
Joseph G. Van Galen,
Rita E. Chen,
Christopher R. Lees,
Sandeep Narpala,
Michael Chambers,
Yaroslav Tsybovsky,
Ulrich Baxa,
Adrian B. McDermott,
John R. Mascola,
Peter D. Kwong
Affiliations
M. Gordon Joyce
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Ivelin S. Georgiev
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Yongping Yang
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Aliaksandr Druz
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Hui Geng
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Gwo-Yu Chuang
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Young Do Kwon
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Marie Pancera
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Reda Rawi
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Mallika Sastry
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Guillaume B.E. Stewart-Jones
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Angela Zheng
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Tongqing Zhou
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Misook Choe
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Joseph G. Van Galen
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Rita E. Chen
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Christopher R. Lees
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Sandeep Narpala
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Michael Chambers
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
Yaroslav Tsybovsky
Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA
Ulrich Baxa
Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA
Adrian B. McDermott
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA
John R. Mascola
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA; Corresponding author
Peter D. Kwong
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA; Corresponding author
Summary: 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. : 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. Keywords: conformational stabilization, envelope trimer, HIV-1 vaccine, prefusion closed trimer, structure-based design
