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- EMDB-25451: pCoV111, a Ferritin-based Nanoparticle Vaccine Candidate Displayi... -

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Entry
Database: EMDB / ID: EMD-25451
TitlepCoV111, a Ferritin-based Nanoparticle Vaccine Candidate Displaying the SARS-CoV-2 Spike S1 Subunit
Map datapCoV111, a Ferritin-based Nanoparticle Vaccine Candidate Displaying the SARS-CoV-2 Spike S1 Subunit
Sample
  • Complex: pCoV111, a Ferritin-based Nanoparticle Vaccine Candidate Displaying the SARS-CoV-2 Spike S1 Subunit
Biological speciesSevere acute respiratory syndrome coronavirus 2
Methodsingle particle reconstruction / negative staining / Resolution: 30.0 Å
AuthorsThomas PV / Smith C / Chen WH / Sankhala RS / Hajduczki A / Choe M / Martinez E / Chang W / Peterson CE / Karch C ...Thomas PV / Smith C / Chen WH / Sankhala RS / Hajduczki A / Choe M / Martinez E / Chang W / Peterson CE / Karch C / Gohain N / Kannadka CB / de Val N / Joyce MG / Modjarrad K
Funding support United States, 2 items
OrganizationGrant numberCountry
Department of Defense (DOD, United States)W81XWH-18-2-0040 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01 AI157155 United States
CitationJournal: bioRxiv / Year: 2021
Title: SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity.
Authors: M Gordon Joyce / Wei-Hung Chen / Rajeshwer S Sankhala / Agnes Hajduczki / Paul V Thomas / Misook Choe / William Chang / Caroline E Peterson / Elizabeth Martinez / Elaine B Morrison / Clayton ...Authors: M Gordon Joyce / Wei-Hung Chen / Rajeshwer S Sankhala / Agnes Hajduczki / Paul V Thomas / Misook Choe / William Chang / Caroline E Peterson / Elizabeth Martinez / Elaine B Morrison / Clayton Smith / Aslaa Ahmed / Lindsay Wieczorek / Alexander Anderson / Rita E Chen / James Brett Case / Yifan Li / Therese Oertel / Lorean Rosado / Akshaya Ganesh / Connor Whalen / Joshua M Carmen / Letzibeth Mendez-Rivera / Christopher Karch / Neelakshi Gohain / Zuzana Villar / David McCurdy / Zoltan Beck / Jiae Kim / Shikha Shrivastava / Ousman Jobe / Vincent Dussupt / Sebastian Molnar / Ursula Tran / Chandrika B Kannadka / Michelle Zemil / Htet Khanh / Weimin Wu / Matthew A Cole / Debra K Duso / Larry W Kummer / Tricia J Lang / Shania E Muncil / Jeffrey R Currier / Shelly J Krebs / Victoria R Polonis / Saravanan Rajan / Patrick M McTamney / Mark T Esser / William W Reiley / Morgane Rolland / Natalia de Val / Michael S Diamond / Gregory D Gromowski / Gary R Matyas / Mangala Rao / Nelson L Michael / Kayvon Modjarrad /
Abstract: The need for SARS-CoV-2 next-generation vaccines has been highlighted by the rise of variants of concern (VoC) and the long-term threat of other coronaviruses. Here, we designed and characterized ...The need for SARS-CoV-2 next-generation vaccines has been highlighted by the rise of variants of concern (VoC) and the long-term threat of other coronaviruses. Here, we designed and characterized four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of prefusion Spike (S), S1 and RBD. These immunogens induced robust S-binding, ACE2-inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2 in mice. A Spike-ferritin nanoparticle (SpFN) vaccine elicited neutralizing titers more than 20-fold higher than convalescent donor serum, following a single immunization, while RBD-Ferritin nanoparticle (RFN) immunogens elicited similar responses after two immunizations. Passive transfer of IgG purified from SpFN- or RFN-immunized mice protected K18-hACE2 transgenic mice from a lethal SARS-CoV-2 virus challenge. Furthermore, SpFN- and RFN-immunization elicited ACE2 blocking activity and neutralizing ID50 antibody titers >2,000 against SARS-CoV-1, along with high magnitude neutralizing titers against major VoC. These results provide design strategies for pan-coronavirus vaccine development.
HIGHLIGHTS: Iterative structure-based design of four Spike-domain Ferritin nanoparticle classes of immunogensSpFN-ALFQ and RFN-ALFQ immunization elicits potent neutralizing activity against SARS-CoV- ...HIGHLIGHTS: Iterative structure-based design of four Spike-domain Ferritin nanoparticle classes of immunogensSpFN-ALFQ and RFN-ALFQ immunization elicits potent neutralizing activity against SARS-CoV-2, variants of concern, and SARS-CoV-1Passively transferred IgG from immunized C57BL/6 mice protects K18-hACE2 mice from lethal SARS-CoV-2 challenge.
History
DepositionNov 19, 2021-
Header (metadata) releaseDec 22, 2021-
Map releaseDec 22, 2021-
UpdateDec 22, 2021-
Current statusDec 22, 2021Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0247
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 0.0247
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_25451.png

Downloads & links

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Map

FileDownload / File: emd_25451.map.gz / Format: CCP4 / Size: 15.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationpCoV111, a Ferritin-based Nanoparticle Vaccine Candidate Displaying the SARS-CoV-2 Spike S1 Subunit
Voxel sizeX=Y=Z: 4.39 Å
Density
Contour LevelBy AUTHOR: 0.0247 / Movie #1: 0.0247
Minimum - Maximum-0.11993967 - 0.08356924
Average (Standard dev.)-0.0010655555 (±0.006538375)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions160160160
Spacing160160160
CellA=B=C: 702.39996 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z4.394.394.39
M x/y/z160160160
origin x/y/z0.0000.0000.000
length x/y/z702.400702.400702.400
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS160160160
D min/max/mean-0.1200.084-0.001

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Supplemental data

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Sample components

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Entire : pCoV111, a Ferritin-based Nanoparticle Vaccine Candidate Displayi...

EntireName: pCoV111, a Ferritin-based Nanoparticle Vaccine Candidate Displaying the SARS-CoV-2 Spike S1 Subunit
Components
  • Complex: pCoV111, a Ferritin-based Nanoparticle Vaccine Candidate Displaying the SARS-CoV-2 Spike S1 Subunit

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Supramolecule #1: pCoV111, a Ferritin-based Nanoparticle Vaccine Candidate Displayi...

SupramoleculeName: pCoV111, a Ferritin-based Nanoparticle Vaccine Candidate Displaying the SARS-CoV-2 Spike S1 Subunit
type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Recombinant expressionOrganism: Homo sapiens (human) / Recombinant cell: Expi293F
Molecular weightTheoretical: 2.3 MDa

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Experimental details

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Structure determination

Methodnegative staining
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration0.05 mg/mL
BufferpH: 7.4 / Details: 1x PBS
StainingType: NEGATIVE / Material: Uranyl Formate

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Electron microscopy

MicroscopeFEI TECNAI 20
Electron beamAcceleration voltage: 200 kV / Electron source: LAB6
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: FEI EAGLE (4k x 4k) / Average electron dose: 50.0 e/Å2

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Image processing

CTF correctionSoftware - Name: CTFFIND (ver. 4.1.14)
Startup modelType of model: INSILICO MODEL / Details: 80 angstrom low pass filter
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.0.8)
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionNumber classes used: 1 / Applied symmetry - Point group: O (octahedral) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 30.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION (ver. 3.0.8) / Number images used: 2121

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