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TitleHIV envelope trimer-elicited autologous neutralizing antibodies bind a region overlapping the N332 glycan supersite.
Journal, issue, pagesSci Adv, Vol. 6, Issue 23, Page eaba0512, Year 2020
Publish dateJun 5, 2020
AuthorsBartek Nogal / Laura E McCoy / Marit J van Gils / Christopher A Cottrell / James E Voss / Raiees Andrabi / Matthias Pauthner / Chi-Hui Liang / Terrence Messmer / Rebecca Nedellec / Mia Shin / Hannah L Turner / Gabriel Ozorowski / Rogier W Sanders / Dennis R Burton / Andrew B Ward /
PubMed AbstractTo date, immunization studies of rabbits with the BG505 SOSIP.664 HIV envelope glycoprotein trimers have revealed the 241/289 glycan hole as the dominant neutralizing antibody epitope. Here, we ...To date, immunization studies of rabbits with the BG505 SOSIP.664 HIV envelope glycoprotein trimers have revealed the 241/289 glycan hole as the dominant neutralizing antibody epitope. Here, we isolated monoclonal antibodies from a rabbit that did not exhibit glycan hole-dependent autologous serum neutralization. The antibodies did not compete with a previously isolated glycan hole-specific antibody but did compete with N332 glycan supersite broadly neutralizing antibodies. A 3.5-Å cryoEM structure of one of the antibodies in complex with the BG505 SOSIP.v5.2 trimer demonstrated that while the epitope recognized overlapped the N332 glycan supersite by contacting the GDIR motif at the base of V3, primary contacts were located in the variable V1 loop. These data suggest that strain-specific responses to V1 may interfere with broadly neutralizing responses to the N332 glycan supersite and vaccine immunogens may require engineering to minimize these off-target responses or steer them toward a more desirable pathway.
External linksSci Adv / PubMed:32548265 / PubMed Central
MethodsEM (single particle)
Resolution3.52 - 25.0 Å
Structure data

EMDB-21256, PDB-6vo0:
BG505 SOSIP.v5.2 in complex with rabbit Fab 43A2
Method: EM (single particle) / Resolution: 3.52 Å

EMDB-21498:
BG505 SOSIP.664 in complex with rabbit Fab 43A2
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-21499:
BG505 SOSIP.664 in complex with rabbit Fab 43A1
Method: EM (single particle) / Resolution: 22.0 Å

EMDB-21500:
BG505 SOSIP.664 in complex with rabbit Fab 43A
Method: EM (single particle) / Resolution: 22.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • oryctolagus cuniculus (rabbit)
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN / HIV / Env / antibody

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