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TitleRecombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 831, Year 2025
Publish dateJan 18, 2025
AuthorsLee Sherry / Mohammad W Bahar / Claudine Porta / Helen Fox / Keith Grehan / Veronica Nasta / Helen M E Duyvesteyn / Luigi De Colibus / Johanna Marsian / Inga Murdoch / Daniel Ponndorf / Seong-Ryong Kim / Sachin Shah / Sarah Carlyle / Jessica J Swanson / Sue Matthews / Clare Nicol / George P Lomonossoff / Andrew J Macadam / Elizabeth E Fry / David I Stuart / Nicola J Stonehouse / David J Rowlands /
PubMed AbstractPolioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines in the mid-1900's, which dramatically reduced disease prevalence. Continued use of ...Polioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines in the mid-1900's, which dramatically reduced disease prevalence. Continued use of these vaccines, however, threatens ultimate disease eradication and achievement of a polio-free world. Virus-like particles (VLPs) that lack a viral genome represent a safer potential vaccine, although they require particle stabilization. Using our previously established genetic techniques to stabilize the structural capsid proteins, we demonstrate production of poliovirus VLPs of all three serotypes, from four different recombinant expression systems. We compare the antigenicity, thermostability and immunogenicity of these stabilized VLPs against the current inactivated polio vaccine, demonstrating equivalent or superior immunogenicity in female Wistar rats. Structural analyses of these recombinant VLPs provide a rational understanding of the stabilizing mutations and the role of potential excipients. Collectively, we have established these poliovirus stabilized VLPs as viable next-generation vaccine candidates for the future.
External linksNat Commun / PubMed:39827284 / PubMed Central
MethodsEM (single particle)
Resolution2.3 - 3.3 Å
Structure data

50064

9eyy

EMDB-50064, PDB-9eyy:
Poliovirus type 1 (strain Mahoney) native conformation stabilised virus-like particle (PV1 SC6b) from a yeast expression system.
Method: EM (single particle) / Resolution: 3.3 Å

50066

9ez0

EMDB-50066, PDB-9ez0:
Poliovirus type 1 (strain Mahoney) expanded conformation stabilised virus-like particle (PV1 SC6b) from a yeast expression system.
Method: EM (single particle) / Resolution: 3.3 Å

50112

9f0k

EMDB-50112, PDB-9f0k:
Poliovirus type 1 (strain Mahoney) expanded conformation stabilised virus-like particle (PV1 SC6b) from a mammalian expression system
Method: EM (single particle) / Resolution: 3.0 Å

50176

9f3q

EMDB-50176, PDB-9f3q:
Poliovirus type 1 (strain Mahoney) stabilised virus-like particle (PV1 SC6b) in complex with GPP3 and GSH.
Method: EM (single particle) / Resolution: 2.75 Å

50189

9f59

EMDB-50189, PDB-9f59:
Poliovirus type 2 (strain MEF-1) stabilised virus-like particle (PV2 SC6b) from a mammalian expression system.
Method: EM (single particle) / Resolution: 2.3 Å

50199

9f5p

EMDB-50199, PDB-9f5p:
Poliovirus type 2 (strain MEF-1) stabilised virus-like particle (PV2 SC6b) from an insect cell expression system.
Method: EM (single particle) / Resolution: 2.6 Å

Chemicals

ChemComp-PLM:
PALMITIC ACID

ChemComp-YM2:
1-[(3S)-5-[4-[(E)-ETHOXYIMINOMETHYL]PHENOXY]-3-METHYL-PENTYL]-3-PYRIDIN-4-YL-IMIDAZOLIDIN-2-ONE

ChemComp-GSH:
GLUTATHIONE

ChemComp-SPH:
SPHINGOSINE

ChemComp-HOH:
WATER

Source
  • human poliovirus 1 mahoney
  • poliovirus 2
KeywordsVIRUS LIKE PARTICLE / Capsid protein / virus-like particle / vaccine / inhibitor / complex

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