6ck9

Publication Abstract from PubMed

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 alpha9-helix and an intersubunit beta 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.

A Universal Approach to Optimize the Folding and Stability of Prefusion-Closed HIV-1 Envelope Trimers.,Rutten L, Lai YT, Blokland S, Truan D, Bisschop IJM, Strokappe NM, Koornneef A, van Manen D, Chuang GY, Farney SK, Schuitemaker H, Kwong PD, Langedijk JPM Cell Rep. 2018 Apr 10;23(2):584-595. doi: 10.1016/j.celrep.2018.03.061. PMID:29642014^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.