Vaccine Potency and Structure of Yeast-Produced Polio Type 2 Stabilized Virus-like Particles

Area of Science:

• Vaccinology
• Structural biology
• Microbial biotechnology

Background:

• Global poliovirus (PV) eradication is nearing completion, driven by oral and inactivated polio vaccines.
• Next-generation vaccines are needed for the post-eradication era, with recombinant virus-like particles (VLPs) showing promise.

Purpose of the Study:

• To evaluate the production, antigenicity, thermostability, immunogenicity, and structure of PV serotype 2 (PV2) VLPs.
• To compare wildtype VLPs (wtVLP) with a thermally stabilized mutant VLP (sVLP) for vaccine potential.

Main Methods:

• Production of PV2 wtVLPs and sVLPs in *Pichia pastoris* yeast.
• Assessment of D-antigen levels, thermostability, and immunogenicity in mouse models.
• Cryo-electron microscopy (cryo-EM) for structural analysis.

Main Results:

• Efficient production of both PV2 wtVLP and sVLP in yeast.
• PV2 sVLP demonstrated superior D-antigen levels and thermostability compared to wtVLP.
• PV2 sVLP elicited neutralizing antibodies comparable to inactivated polio vaccine, with enhanced response when adjuvanted.

Conclusions:

• Yeast-produced PV2 sVLP is a viable and promising vaccine candidate with high production potential.
• Structural insights reveal the native conformation of sVLP contributes to its enhanced immunogenicity.
• Findings support the development of sVLP-based poliovirus vaccines.