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- PDB-9mml: RB1 Fab bound to 1A6 anti-idiotype Fab -

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Basic information

Entry
Database: PDB / ID: 9mml
TitleRB1 Fab bound to 1A6 anti-idiotype Fab
Components
  • 1A6 heavy chain
  • 1A6 light chain
  • RB1 heavy chain
  • RB1 light chain
KeywordsIMMUNE SYSTEM / Fab anti idiotype RSV
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.67 Å
AuthorsWarren, C.
Funding support1items
OrganizationGrant numberCountry
Other private
CitationJournal: Vaccines (Basel) / Year: 2025
Title: Anti-Idiotypic Antibody as a Booster Vaccine Against Respiratory Syncytial Virus.
Authors: Shreya Mukhopadhyay / Ioannis Manolaridis / Christopher Warren / Aimin Tang / Gregory O'Donnell / Bin Luo / Ryan P Staupe / Kalpit A Vora / Zhifeng Chen /
Abstract: The respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children and adults. With nearly everyone infected by the age of five, there is an opportunity to ... The respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children and adults. With nearly everyone infected by the age of five, there is an opportunity to develop booster vaccines that enhance B-cell immunity, promoting potent and broadly neutralizing antibodies. One potential approach involves using anti-idiotypic antibodies (anti-IDs) to mimic specific antigenic sites and enhance preexisting immunity in an epitope-specific manner. RB1, a monoclonal antibody (mAb) that binds to site IV of the RSV fusion (RSV F) protein, is a potent and broadly neutralizing against RSV A and B viruses. It is the precursor for MK1654 (clesrovimab), which successfully completed a Phase III clinical trial. In this study, we isolated two anti-IDs, 1A6 and 1D4, targeting RB1 CDR regions, demonstrating that 1A6 competes fully with RSV F in binding to RB1. We resolved the RB1-1A6 and RB1-1D4 Fab-Fab complex structures and proved that 1A6 mimics the RSV F site IV better than 1D4. In an immunogenicity study, mice primed with RSV F and boosted with 1A6 Fab showed a site IV-specific antibody response with a concurrent increase in RSV virus neutralization. These results suggest that anti-IDs could be potentially used as booster vaccines for specific epitopes.
History
DepositionDec 20, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 8, 2025Provider: repository / Type: Initial release
Revision 1.1Feb 5, 2025Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.pdbx_database_id_PubMed / _citation.title / _em_admin.last_update

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
H: 1A6 heavy chain
L: 1A6 light chain
M: RB1 heavy chain
N: RB1 light chain


Theoretical massNumber of molelcules
Total (without water)94,2504
Polymers94,2504
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Antibody 1A6 heavy chain


Mass: 23557.316 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): CHO / Production host: Cricetulus griseus (Chinese hamster)
#2: Antibody 1A6 light chain


Mass: 22735.072 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): CHO / Production host: Cricetulus griseus (Chinese hamster)
#3: Antibody RB1 heavy chain


Mass: 24551.439 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): CHO / Production host: Cricetulus griseus (Chinese hamster)
#4: Antibody RB1 light chain


Mass: 23406.043 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): CHO / Production host: Cricetulus griseus (Chinese hamster)
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: RB1 Fab bound to 1A6 anti-idiotype Fab / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Cricetulus griseus (Chinese hamster)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 600 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 11590

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.67 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 689729 / Symmetry type: POINT
Atomic model buildingProtocol: AB INITIO MODEL
RefinementHighest resolution: 3.67 Å / Cross valid method: NONE
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0055199
ELECTRON MICROSCOPYf_angle_d0.6926871
ELECTRON MICROSCOPYf_dihedral_angle_d4.825907
ELECTRON MICROSCOPYf_chiral_restr0.047529
ELECTRON MICROSCOPYf_plane_restr0.0051026

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