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• W2798224102 abstract "The heavily glycosylated native-like envelope (Env) trimer of HIV-1 is expected to have low immunogenicity, whereas misfolded forms are often highly immunogenic. High-quality correctly folded Envs may therefore be critical for developing a vaccine that induces broadly neutralizing antibodies. Moreover, the high variability of Env may require immunizations with multiple Envs. Here, we report a universal strategy that provides for correctly folded Env trimers of high quality and yield through a repair-and-stabilize approach. In the repair stage, we utilized a consensus strategy that substituted rare strain-specific residues with more prevalent ones. The stabilization stage involved structure-based design and experimental assessment confirmed by crystallographic feedback. Regions important for the refolding of Env were targeted for stabilization. Notably, the α9-helix and an intersubunit β sheet proved to be critical for trimer stability. Our approach provides a means to produce prefusion-closed Env trimers from diverse HIV-1 strains, a substantial advance for vaccine development." @default.
• W2798224102 created "2018-04-24" @default.
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• W2798224102 date "2018-04-01" @default.
• W2798224102 modified "2023-10-03" @default.
• W2798224102 title "A Universal Approach to Optimize the Folding and Stability of Prefusion-Closed HIV-1 Envelope Trimers" @default.
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• W2798224102 doi "https://doi.org/10.1016/j.celrep.2018.03.061" @default.
• W2798224102 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6010203" @default.
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• W2798224102 hasPublicationYear "2018" @default.
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