[English] 日本語
Yorodumi- EMDB-40257: BG505 MD39 SOSIP in complex with Rh.NJ77 wk12 V1V3, C3V5, N611/FP... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-40257 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | BG505 MD39 SOSIP in complex with Rh.NJ77 wk12 V1V3, C3V5, N611/FP and base epitope polyclonal | |||||||||
Map data | main map (base antibody) | |||||||||
Sample |
| |||||||||
Keywords | polyclonal antibodies / EMPEM / HIV-1 / vaccine / non-human primate / Env / VIRAL PROTEIN | |||||||||
Biological species | Macaca mulatta (Rhesus monkey) / Human immunodeficiency virus 1 | |||||||||
Method | single particle reconstruction / negative staining / Resolution: 28.0 Å | |||||||||
Authors | Lee WS / Ozorowski G / Torres JL / Ward AB | |||||||||
Funding support | United States, 1 items
| |||||||||
Citation | Journal: Nat Commun / Year: 2023 Title: A combined adjuvant approach primes robust germinal center responses and humoral immunity in non-human primates. Authors: Ivy Phung / Kristen A Rodrigues / Ester Marina-Zárate / Laura Maiorino / Bapi Pahar / Wen-Hsin Lee / Mariane Melo / Amitinder Kaur / Carolina Allers / Marissa Fahlberg / Brooke F Grasperge ...Authors: Ivy Phung / Kristen A Rodrigues / Ester Marina-Zárate / Laura Maiorino / Bapi Pahar / Wen-Hsin Lee / Mariane Melo / Amitinder Kaur / Carolina Allers / Marissa Fahlberg / Brooke F Grasperge / Jason P Dufour / Faith Schiro / Pyone P Aye / Paul G Lopez / Jonathan L Torres / Gabriel Ozorowski / Saman Eskandarzadeh / Michael Kubitz / Erik Georgeson / Bettina Groschel / Rebecca Nedellec / Michael Bick / Katarzyna Kaczmarek Michaels / Hongmei Gao / Xiaoying Shen / Diane G Carnathan / Guido Silvestri / David C Montefiori / Andrew B Ward / Lars Hangartner / Ronald S Veazey / Dennis R Burton / William R Schief / Darrell J Irvine / Shane Crotty / Abstract: Adjuvants and antigen delivery kinetics can profoundly influence B cell responses and should be critically considered in rational vaccine design, particularly for difficult neutralizing antibody ...Adjuvants and antigen delivery kinetics can profoundly influence B cell responses and should be critically considered in rational vaccine design, particularly for difficult neutralizing antibody targets such as human immunodeficiency virus (HIV). Antigen kinetics can change depending on the delivery method. To promote extended immunogen bioavailability and to present antigen in a multivalent form, native-HIV Env trimers are modified with short phosphoserine peptide linkers that promote tight binding to aluminum hydroxide (pSer:alum). Here we explore the use of a combined adjuvant approach that incorporates pSer:alum-mediated antigen delivery with potent adjuvants (SMNP, 3M-052) in an extensive head-to-head comparison study with conventional alum to assess germinal center (GC) and humoral immune responses. Priming with pSer:alum plus SMNP induces additive effects that enhance the magnitude and persistence of GCs, which correlate with better GC-T cell help. Autologous HIV-neutralizing antibody titers are improved in SMNP-immunized animals after two immunizations. Over 9 months after priming immunization of pSer:alum with either SMNP or 3M-052, robust Env-specific bone marrow plasma cells (BM B) are observed. Furthermore, pSer-modification of Env trimer reduce targeting towards immunodominant non-neutralizing epitopes. The study shows that a combined adjuvant approach can augment humoral immunity by modulating immunodominance and shows promise for clinical translation. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_40257.map.gz | 20.6 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-40257-v30.xml emd-40257.xml | 23.6 KB 23.6 KB | Display Display | EMDB header |
Images | emd_40257.png | 65.7 KB | ||
Filedesc metadata | emd-40257.cif.gz | 4.9 KB | ||
Others | emd_40257_additional_1.map.gz emd_40257_additional_2.map.gz emd_40257_additional_3.map.gz emd_40257_half_map_1.map.gz emd_40257_half_map_2.map.gz | 20.6 MB 20.6 MB 6.1 MB 20.6 MB 20.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40257 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40257 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|
-Map
File | Download / File: emd_40257.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | main map (base antibody) | ||||||||||||||||||||
Voxel size | X=Y=Z: 2.06 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Additional map: Additional map 1: N611/FP antibody
File | emd_40257_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Additional map 1: N611/FP antibody | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: Additional map 2: C3V5 antibody
File | emd_40257_additional_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Additional map 2: C3V5 antibody | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: Additional map 3: V1V3 and base antibodies
File | emd_40257_additional_3.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Additional map 3: V1V3 and base antibodies | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map A
File | emd_40257_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map A | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map B
File | emd_40257_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map B | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : BG505 MD39 SOSIP in complex with Rh.NJ77 wk12 V1V3, C3V5, N611/FP...
Entire | Name: BG505 MD39 SOSIP in complex with Rh.NJ77 wk12 V1V3, C3V5, N611/FP and base epitope polyclonal |
---|---|
Components |
|
-Supramolecule #1: BG505 MD39 SOSIP in complex with Rh.NJ77 wk12 V1V3, C3V5, N611/FP...
Supramolecule | Name: BG505 MD39 SOSIP in complex with Rh.NJ77 wk12 V1V3, C3V5, N611/FP and base epitope polyclonal type: complex / ID: 1 / Parent: 0 Details: Polyclonal antibodies isolated from serum of non-human primates, digested to Fab, and complexed with HIV-1 BG505 MD39 SOSIP.664 Env |
---|
-Supramolecule #2: Rh.NJ77 wk12 V1V3, C3V5, N611/FP and base epitope polyclonal
Supramolecule | Name: Rh.NJ77 wk12 V1V3, C3V5, N611/FP and base epitope polyclonal type: complex / ID: 2 / Parent: 1 |
---|---|
Source (natural) | Organism: Macaca mulatta (Rhesus monkey) |
-Supramolecule #3: BG505 MD39 SOSIP
Supramolecule | Name: BG505 MD39 SOSIP / type: complex / ID: 3 / Parent: 1 |
---|---|
Source (natural) | Organism: Human immunodeficiency virus 1 |
-Experimental details
-Structure determination
Method | negative staining |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.02 mg/mL |
---|---|
Buffer | pH: 7.4 |
Staining | Type: NEGATIVE / Material: Uranyl formate / Details: 2% w/v uranyl formate |
Grid | Model: Homemade / Support film - Material: PARLODION |
-Electron microscopy
Microscope | FEI TECNAI SPIRIT |
---|---|
Electron beam | Acceleration voltage: 120 kV / Electron source: LAB6 |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.0 µm |
Image recording | Film or detector model: FEI EAGLE (4k x 4k) / Average electron dose: 25.0 e/Å2 |
Experimental equipment | Model: Tecnai Spirit / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: Details: simulated map generated from PDB coordinates and low pass filtered |
---|---|
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 28.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 3214 |