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- EMDB-41474: H2 hemagglutinin (A/Singapore/1/1957) in complex with polyclonal ... -

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Entry
Database: EMDB / ID: EMD-41474
TitleH2 hemagglutinin (A/Singapore/1/1957) in complex with polyclonal Fab, pAb_3
Map dataH2 hemagglutinin (A/Singapore/1/1957) in complex with polyclonal Fab, pAb_3
Sample
  • Complex: H2 hemagglutinin (A/Singapore/1/1957) in complex with polyclonal Fab, pAb_3
Keywordsinfluenza / hemagglutinin / monoclonal antibody / immune complex / VIRAL PROTEIN
Biological speciesInfluenza A virus (A/Singapore/1/1957(H2N2))
Methodsingle particle reconstruction / cryo EM / Resolution: 6.1 Å
AuthorsYang YR / Han J / Perrett HR / Ward AB
Funding support United States, 3 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-004923 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)2 T32 AI007244-36 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)1F31Al172358 United States
CitationJournal: Cell Rep / Year: 2024
Title: Immune memory shapes human polyclonal antibody responses to H2N2 vaccination.
Authors: Yuhe R Yang / Julianna Han / Hailee R Perrett / Sara T Richey / Alesandra J Rodriguez / Abigail M Jackson / Rebecca A Gillespie / Sarah O'Connell / Julie E Raab / Lauren Y Cominsky / Ankita ...Authors: Yuhe R Yang / Julianna Han / Hailee R Perrett / Sara T Richey / Alesandra J Rodriguez / Abigail M Jackson / Rebecca A Gillespie / Sarah O'Connell / Julie E Raab / Lauren Y Cominsky / Ankita Chopde / Masaru Kanekiyo / Katherine V Houser / Grace L Chen / Adrian B McDermott / Sarah F Andrews / Andrew B Ward /
Abstract: Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. A recent phase 1 clinical trial investigating a ferritin nanoparticle vaccine displaying H2 ...Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. A recent phase 1 clinical trial investigating a ferritin nanoparticle vaccine displaying H2 hemagglutinin (HA) in H2-naive and H2-exposed adults enabled us to perform comprehensive structural and biochemical characterization of immune memory on the breadth and diversity of the polyclonal serum antibody response elicited. We temporally map the epitopes targeted by serum antibodies after vaccine prime and boost, revealing that previous H2 exposure results in higher responses to the variable HA head domain. In contrast, initial responses in H2-naive participants are dominated by antibodies targeting conserved epitopes. We use cryoelectron microscopy and monoclonal B cell isolation to describe the molecular details of cross-reactive antibodies targeting conserved epitopes on the HA head, including the receptor-binding site and a new site of vulnerability deemed the medial junction. Our findings accentuate the impact of pre-existing influenza exposure on serum antibody responses post-vaccination.
History
DepositionAug 4, 2023-
Header (metadata) releaseOct 11, 2023-
Map releaseOct 11, 2023-
UpdateFeb 26, 2025-
Current statusFeb 26, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_41474.png

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Map

FileDownload / File: emd_41474.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationH2 hemagglutinin (A/Singapore/1/1957) in complex with polyclonal Fab, pAb_3
Projections & slices

Image control

Size
Brightness
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AxesZ (Sec.)Y (Row.)X (Col.)
1.15 Å/pix.
x 320 pix.
= 368. Å		1.15 Å/pix.
x 320 pix.
= 368. Å		1.15 Å/pix.
x 320 pix.
= 368. Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.15 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0046
Minimum - Maximum-0.009710209 - 0.03300004
Average (Standard dev.)-0.00000018042478 (±0.00087331526)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 368.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_41474_msk_1.map
Projections & Slices
AxesZYX

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Half map: Half Map 1

Fileemd_41474_half_map_1.map
AnnotationHalf Map 1
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Half map: Half Map 2

Fileemd_41474_half_map_2.map
AnnotationHalf Map 2
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Sample components

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Entire : H2 hemagglutinin (A/Singapore/1/1957) in complex with polyclonal ...

EntireName: H2 hemagglutinin (A/Singapore/1/1957) in complex with polyclonal Fab, pAb_3
Components
  • Complex: H2 hemagglutinin (A/Singapore/1/1957) in complex with polyclonal Fab, pAb_3

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Supramolecule #1: H2 hemagglutinin (A/Singapore/1/1957) in complex with polyclonal ...

SupramoleculeName: H2 hemagglutinin (A/Singapore/1/1957) in complex with polyclonal Fab, pAb_3
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Influenza A virus (A/Singapore/1/1957(H2N2))

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.3 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.7000000000000001 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

2wr7

Final reconstructionResolution.type: BY AUTHOR / Resolution: 6.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 17933
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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