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Yorodumi- EMDB-24854: Modified BG505 SOSIP-based immunogen RC1 in complex with elicited... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24854 | |||||||||
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Title | Modified BG505 SOSIP-based immunogen RC1 in complex with elicited mAb Ab1170NHP Fab and 8ANC195 Fab | |||||||||
Map data | ||||||||||
Sample |
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Biological species | Macaca mulatta (Rhesus monkey) / Human immunodeficiency virus 1 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.5 Å | |||||||||
Authors | Abernathy ME / Bjorkman PJ | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Sci Transl Med / Year: 2021 Title: Sequential immunization of macaques elicits heterologous neutralizing antibodies targeting the V3-glycan patch of HIV-1 Env. Authors: Amelia Escolano / Harry B Gristick / Rajeev Gautam / Andrew T DeLaitsch / Morgan E Abernathy / Zhi Yang / Haoqing Wang / Magnus A G Hoffmann / Yoshiaki Nishimura / Zijun Wang / Nicholas ...Authors: Amelia Escolano / Harry B Gristick / Rajeev Gautam / Andrew T DeLaitsch / Morgan E Abernathy / Zhi Yang / Haoqing Wang / Magnus A G Hoffmann / Yoshiaki Nishimura / Zijun Wang / Nicholas Koranda / Leesa M Kakutani / Han Gao / Priyanthi N P Gnanapragasam / Henna Raina / Ana Gazumyan / Melissa Cipolla / Thiago Y Oliveira / Victor Ramos / Darrell J Irvine / Murillo Silva / Anthony P West / Jennifer R Keeffe / Christopher O Barnes / Michael S Seaman / Michel C Nussenzweig / Malcolm A Martin / Pamela J Bjorkman / Abstract: Broadly neutralizing antibodies (bNAbs) against HIV-1 develop after prolonged virus and antibody coevolution. Previous studies showed that sequential immunization with a V3-glycan patch germline- ...Broadly neutralizing antibodies (bNAbs) against HIV-1 develop after prolonged virus and antibody coevolution. Previous studies showed that sequential immunization with a V3-glycan patch germline-targeting HIV-1 envelope trimer (Env) followed by variant Envs can reproduce this process in mice carrying V3-glycan bNAb precursor B cells. However, eliciting bNAbs in animals with polyclonal antibody repertoires is more difficult. We used a V3-glycan immunogen multimerized on virus-like particles (VLPs), followed by boosting with increasingly native-like Env-VLPs, to elicit heterologous neutralizing antibodies in nonhuman primates (NHPs). Structures of antibody/Env complexes after prime and boost vaccinations demonstrated target epitope recognition with apparent maturation to accommodate glycans. However, we also observed increasing off-target antibodies with boosting. Eight vaccinated NHPs were subsequently challenged with simian-human immunodeficiency virus (SHIV), and seven of eight animals became infected. The single NHP that remained uninfected after viral challenge exhibited one of the lowest neutralization titers against the challenge virus. These results demonstrate that more potent heterologous neutralization resulting from sequential immunization is necessary for protection in this animal model. Thus, improved prime-boost regimens to increase bNAb potency and stimulate other immune protection mechanisms are essential for developing anti–HIV-1 vaccines. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_24854.map.gz | 121.5 MB | EMDB map data format | |
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Header (meta data) | emd-24854-v30.xml emd-24854.xml | 18.1 KB 18.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_24854_fsc.xml | 11.6 KB | Display | FSC data file |
Images | emd_24854.png | 175 KB | ||
Masks | emd_24854_msk_1.map | 129.7 MB | Mask map | |
Others | emd_24854_additional_1.map.gz emd_24854_half_map_1.map.gz emd_24854_half_map_2.map.gz | 121.2 MB 39.8 MB 39.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24854 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24854 | HTTPS FTP |
-Validation report
Summary document | emd_24854_validation.pdf.gz | 507 KB | Display | EMDB validaton report |
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Full document | emd_24854_full_validation.pdf.gz | 506.6 KB | Display | |
Data in XML | emd_24854_validation.xml.gz | 19 KB | Display | |
Data in CIF | emd_24854_validation.cif.gz | 24.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24854 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24854 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_24854.map.gz / Format: CCP4 / Size: 129.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.8972 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_24854_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: #1
File | emd_24854_additional_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_24854_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_24854_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Elicited Ab1170NHP Fab in complex with immunogen RC1 SOSIP and bN...
Entire | Name: Elicited Ab1170NHP Fab in complex with immunogen RC1 SOSIP and bNAb 8ANC195 Fab |
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Components |
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-Supramolecule #1: Elicited Ab1170NHP Fab in complex with immunogen RC1 SOSIP and bN...
Supramolecule | Name: Elicited Ab1170NHP Fab in complex with immunogen RC1 SOSIP and bNAb 8ANC195 Fab type: complex / ID: 1 / Parent: 0 |
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Molecular weight | Theoretical: 600 KDa |
-Supramolecule #2: Ab1170NHP Fab
Supramolecule | Name: Ab1170NHP Fab / type: complex / ID: 2 / Parent: 1 |
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Source (natural) | Organism: Macaca mulatta (Rhesus monkey) |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: RC1 SOSIP
Supramolecule | Name: RC1 SOSIP / type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #4: 8ANC195 Fab
Supramolecule | Name: 8ANC195 Fab / type: complex / ID: 4 / Parent: 1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.4 mg/mL |
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Buffer | pH: 8 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 1151 / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal magnification: 45000 |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |