|Entry||Database: EMDB / ID: EMD-0571|
|Title||HIV-1 vaccine elicited polyclonal 145-11 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2|
|Sample||HIV-1 vaccine elicited Fab in complex with the HIV Env trimer BG505 SOSIPv5.2:|
SOSIP trimer / Polyclonal Fab
|Biological species||Homo sapiens (human) / Macaca (macaques)|
|Method||single particle reconstruction / Resolution: 18.45 Å|
|Authors||Nogal B / Ward AB|
|Citation||Journal: Cell / Year: 2019|
Title: Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance.
Authors: Kimberly M Cirelli / Diane G Carnathan / Bartek Nogal / Jacob T Martin / Oscar L Rodriguez / Amit A Upadhyay / Chiamaka A Enemuo / Etse H Gebru / Yury Choe / Federico Viviano / Catherine Nakao / Matthias G Pauthner / Samantha Reiss / Christopher A Cottrell / Melissa L Smith / Raiza Bastidas / William Gibson / Amber N Wolabaugh / Mariane B Melo / Benjamin Cossette / Venkatesh Kumar / Nirav B Patel / Talar Tokatlian / Sergey Menis / Daniel W Kulp / Dennis R Burton / Ben Murrell / William R Schief / Steven E Bosinger / Andrew B Ward / Corey T Watson / Guido Silvestri / Darrell J Irvine / Shane Crotty /
Abstract: Conventional immunization strategies will likely be insufficient for the development of a broadly neutralizing antibody (bnAb) vaccine for HIV or other difficult pathogens because of the ...Conventional immunization strategies will likely be insufficient for the development of a broadly neutralizing antibody (bnAb) vaccine for HIV or other difficult pathogens because of the immunological hurdles posed, including B cell immunodominance and germinal center (GC) quantity and quality. We found that two independent methods of slow delivery immunization of rhesus monkeys (RMs) resulted in more robust T follicular helper (T) cell responses and GC B cells with improved Env-binding, tracked by longitudinal fine needle aspirates. Improved GCs correlated with the development of >20-fold higher titers of autologous nAbs. Using a new RM genomic immunoglobulin locus reference, we identified differential IgV gene use between immunization modalities. Ab mapping demonstrated targeting of immunodominant non-neutralizing epitopes by conventional bolus-immunized animals, whereas slow delivery-immunized animals targeted a more diverse set of epitopes. Thus, alternative immunization strategies can enhance nAb development by altering GCs and modulating the immunodominance of non-neutralizing epitopes.
|Date||Deposition: Feb 16, 2019 / Header (metadata) release: Feb 27, 2019 / Map release: May 29, 2019 / Update: May 29, 2019|
|Structure viewer||EM map: |
Downloads & links
|File||Download / File: emd_0571.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 HIV-1 vaccine elicited Fab in complex with the HIV Env trimer BG5...
|Entire||Name: HIV-1 vaccine elicited Fab in complex with the HIV Env trimer BG505 SOSIPv5.2|
Number of components: 3
-Component #1: protein, HIV-1 vaccine elicited Fab in complex with the HIV Env t...
|Protein||Name: HIV-1 vaccine elicited Fab in complex with the HIV Env trimer BG505 SOSIPv5.2|
Recombinant expression: No
-Component #2: protein, SOSIP trimer
|Protein||Name: SOSIP trimer / Recombinant expression: No|
|Source||Species: Homo sapiens (human)|
-Component #3: protein, Polyclonal Fab
|Protein||Name: Polyclonal Fab / Recombinant expression: No|
|Source||Species: Macaca (macaques)|
|Specimen||Specimen state: Particle|
|Sample solution||pH: 7.4|
|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: SIDE ENTRY, EUCENTRIC|
|Image acquisition||Sampling size: 14 µm|
|Processing||Method: single particle reconstruction / Number of projections: 7382|
|3D reconstruction||Software: RELION / Resolution: 18.45 Å / Resolution method: FSC 0.143 CUT-OFF|
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