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TitleHoles in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies.
Journal, issue, pagesCell Rep, Vol. 16, Issue 9, Page 2327-2338, Year 2016
Publish dateAug 30, 2016
AuthorsLaura E McCoy / Marit J van Gils / Gabriel Ozorowski / Terrence Messmer / Bryan Briney / James E Voss / Daniel W Kulp / Matthew S Macauley / Devin Sok / Matthias Pauthner / Sergey Menis / Christopher A Cottrell / Jonathan L Torres / Jessica Hsueh / William R Schief / Ian A Wilson / Andrew B Ward / Rogier W Sanders / Dennis R Burton /
PubMed AbstractA major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP.664) that can induce robust autologous Tier 2 neutralization. Here, potently ...A major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP.664) that can induce robust autologous Tier 2 neutralization. Here, potently neutralizing monoclonal antibodies (nAbs) from rabbits immunized with BG505 SOSIP.664 are shown to recognize an immunodominant region of gp120 centered on residue 241. Residue 241 occupies a hole in the glycan defenses of the BG505 isolate, with fewer than 3% of global isolates lacking a glycan site at this position. However, at least one conserved glycan site is missing in 89% of viruses, suggesting the presence of glycan holes in most HIV isolates. Serum evidence is consistent with targeting of holes in natural infection. The immunogenic nature of breaches in the glycan shield has been under-appreciated in previous attempts to understand autologous neutralizing antibody responses and has important potential consequences for HIV vaccine design.
External linksCell Rep / PubMed:27545891 / PubMed Central
MethodsEM (single particle)
Resolution20.0 - 22.0 Å
Structure data

EMDB-8309:
HIV-1 Env BG505 SOSIP.664 trimer in complex with 2 copies of rabbit antibody 12A fragment antigen binding
Method: EM (single particle) / Resolution: 22.0 Å

EMDB-8310:
HIV-1 Env BG505 SOSIP.664 trimer in complex with 3 copies of rabbit antibody 11B fragment antigen binding
Method: EM (single particle) / Resolution: 22.0 Å

EMDB-8311:
HIV-1 Env BG505 SOSIP.664 trimer in complex with 3 copies of rabbit antibody 11A fragment antigen binding
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-8312:
HIV-1 Env BG505 SOSIP.664 trimer in complex with 3 copies of rabbit antibody 10A fragment antigen binding
Method: EM (single particle) / Resolution: 20.0 Å

Source
  • Oryctolagus cuniculus (rabbit)
  • Human immunodeficiency virus 1

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