|Entry||Database: EMDB / ID: EMD-22387|
|Title||Monoclonal Rh046.7 from animal 12-046|
|Sample||Rh046.7 monoclonal complexed with BG505v3 trimer|
|Biological species||Macaca mulatta (Rhesus monkey)|
|Method||single particle reconstruction / negative staining / Resolution: 17.4 Å|
|Authors||Nogal B / Cottrell CA / Ward AB|
|Funding support|| United States, 2 items |
|Citation||Journal: Cell Rep / Year: 2020|
Title: Mapping Neutralizing Antibody Epitope Specificities to an HIV Env Trimer in Immunized and in Infected Rhesus Macaques.
Authors: Fangzhu Zhao / Collin Joyce / Alison Burns / Bartek Nogal / Christopher A Cottrell / Alejandra Ramos / Trevor Biddle / Matthias Pauthner / Rebecca Nedellec / Huma Qureshi / Rosemarie Mason / ...Authors: Fangzhu Zhao / Collin Joyce / Alison Burns / Bartek Nogal / Christopher A Cottrell / Alejandra Ramos / Trevor Biddle / Matthias Pauthner / Rebecca Nedellec / Huma Qureshi / Rosemarie Mason / Elise Landais / Bryan Briney / Andrew B Ward / Dennis R Burton / Devin Sok /
Abstract: BG505 SOSIP is a well-characterized near-native recombinant HIV Envelope (Env) trimer that holds promise as part of a sequential HIV immunogen regimen to induce broadly neutralizing antibodies (bnAbs) ...BG505 SOSIP is a well-characterized near-native recombinant HIV Envelope (Env) trimer that holds promise as part of a sequential HIV immunogen regimen to induce broadly neutralizing antibodies (bnAbs). Rhesus macaques are considered the most appropriate pre-clinical animal model for monitoring antibody (Ab) responses. Accordingly, we report here the isolation of 45 BG505 autologous neutralizing antibodies (nAbs) with multiple specificities from SOSIP-immunized and BG505 SHIV-infected rhesus macaques. We associate the most potent neutralization with two epitopes: the C3/V5 and V1/V3 regions. We show that all of the nAbs bind in close proximity to known bnAb epitopes and might therefore sterically hinder elicitation of bnAbs. We also identify a "public clonotype" that targets the immunodominant C3/V5 nAb epitope, which suggests that common antibody rearrangements might help determine humoral responses to Env immunogens. The results highlight important considerations for vaccine design in anticipation of results of the BG505 SOSIP trimer in clinical trials.
|Structure viewer||EM map: |
Downloads & links
|File||Download / File: emd_22387.map.gz / Format: CCP4 / Size: 11.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 2.05 Å|
|Symmetry||Space group: 1|
CCP4 map header:
-Entire Rh046.7 monoclonal complexed with BG505v3 trimer
|Entire||Name: Rh046.7 monoclonal complexed with BG505v3 trimer / Number of components: 1|
-Component #1: protein, Rh046.7 monoclonal complexed with BG505v3 trimer
|Protein||Name: Rh046.7 monoclonal complexed with BG505v3 trimer / Recombinant expression: No|
|Source||Species: Macaca mulatta (Rhesus monkey)|
|Source (engineered)||Expression System: Homo sapiens (human)|
|Specimen||Specimen state: Particle / Method: negative staining|
|Sample solution||pH: 5.5|
|Vitrification||Cryogen name: NONE|
-Electron microscopy imaging
|Imaging||Microscope: FEI TECNAI 12|
|Electron gun||Electron source: LAB6 / Accelerating voltage: 120 kV / Electron dose: 25 e/Å2 / Illumination mode: FLOOD BEAM|
|Lens||Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: OTHER|
|Processing||Method: single particle reconstruction / Number of projections: 5100|
|3D reconstruction||Resolution: 17.4 Å / Resolution method: FSC 0.143 CUT-OFF|
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