Structure-Based Stabilization of SOSIP Env Enhances Recombinant Ectodomain Durability and Yield
Daniel Wrapp, Zekun Mu, Bhishem Thakur, Katarzyna Janowska, Oluwatobi Ajayi, Maggie Barr, Robert Parks, Katayoun Mansouri, Robert J. Edwards, Beatrice H. Hahn, Priyamvada Acharya, Kevin O. Saunders, Barton F. Haynes
Abstract
Recent estimates have placed the number of new human immunodeficiency virus type 1 (HIV-1) infections at approximately 1.5 million per year, emphasizing the ongoing and urgent need for an effective vaccine. The envelope (Env) glycoprotein is the main focus of HIV-1 vaccine development, but, due to its inherent metastability, many Env variants are difficult to recombinantly express in the relatively large quantities that are required for biochemical studies and animal trials. Here, we describe a novel structure-based stabilization strategy that works synergistically with previously described SOSIP mutations to increase the yield of prefusion HIV-1 Env.