Abstract
Advances in HIV-1 envelope glycoprotein (Env) design generate native-like trimers and high-resolution clade A, B, and G structures and elicit neutralizing antibodies. However, a high-resolution clade C structure is critical, as this subtype accounts for the majority of HIV infections worldwide, but well-ordered clade C Env trimers are more challenging to produce due to their instability. Based on targeted glycine substitutions in the Env fusion machinery, we defined a general approach that disfavors helical transitions leading to post-fusion conformations, thereby favoring the pre-fusion state. We generated a stabilized, soluble clade C Env (16055 NFL) and determined its crystal structure at 3.9 Å. Its overall conformation is similar to SOSIP.664 and native Env trimers but includes a covalent linker between gp120 and gp41, an engineered 201-433 disulfide bond, and density corresponding to 22 N-glycans. Env-structure-guided design strategies resulted in multiple homogeneous cross-clade immunogens with the potential to advance HIV vaccine development.
Original language | English (US) |
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Pages (from-to) | 792-803.e3 |
Journal | Immunity |
Volume | 46 |
Issue number | 5 |
DOIs | |
State | Published - May 16 2017 |
Keywords
- Antibody
- Envelope glycoprotein
- Glycan shield
- HIV
- Immunogen
- Trimer
- Vaccine
- bNAb
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases