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TitleHigh-yield production of immunogenic PV3 virus-like particle in yeast.
Journal, issue, pagesAntiviral Res, Vol. 255, Page 106530, Year 2026
Publish dateSep 4, 2026
AuthorsTian Chen / Qin Hong / Wenyu Han / Shuxia Wang / Cheng Lin / Jiaqi Yao / Chaoyang Lian / Qingwei Liu / Xiaoli Wang / Yanqiu Zhou / Yao Cong / Zhong Huang /
PubMed AbstractThe identification of thermally stabilized mutants of all three poliovirus serotypes (PV1, PV2, and PV3) has enabled the development of virus-like particle (VLP)-based next-generation poliovirus ...The identification of thermally stabilized mutants of all three poliovirus serotypes (PV1, PV2, and PV3) has enabled the development of virus-like particle (VLP)-based next-generation poliovirus vaccines. PV3 stabilized mutant-derived VLPs (sVLPs) have been produced in several recombinant systems through co-expression of mutant P1 polyprotein with native or uncleavable viral protease 3CD, and have shown immunogenicity in animal models. However, their yields remain suboptimal, likely because of intrinsic 3CD toxicity and/or inefficient 3CD-mediated cleavage of P1 into capsid subunits VP0, VP3, and VP1, creating a bottleneck for cost-effective product development. In this study, we designed a protease-independent expression strategy based on simultaneous co-expression of VP0, VP3, and VP1 capsid subunit (VP0/VP3/VP1) and compared it with the conventional P1/3CD co-expression approach for production of PV3 sVLP and wildtype VLP (wtVLP) in Pichia pastoris. For each VLP type, the VP0/VP3/VP1 strategy in general enhances target protein expression and D-antigen formation compared with P1/3CD co-expression. The PV3 sVLP produced by the VP0/VP3/VP1 strategy possesses higher levels of D-antigen and significantly enhanced thermostability than the corresponding wtVLP. Moreover, structural and immunological analyses reveal that PV3 sVLP, but not wtVLP, adopts a native conformation and potently elicits neutralizing antibodies in a mouse model. These findings not only confirm yeast-produced PV3 sVLP as a promising vaccine candidate, but also establish a high-yield and scalable expression strategy amenable to further development and industrial-level production of sVLP-based next-generation polio vaccines.
External linksAntiviral Res / PubMed:42692371
MethodsEM (single particle)
Resolution2.76 - 2.87 Å
Structure data

EMDB-81988, PDB-43mi:
Yeast-expressed polio type 3 stabilized virus-like particles
Method: EM (single particle) / Resolution: 2.87 Å

EMDB-81997, PDB-43mu:
Yeast-expressed polio type 3 expanded virus-like particles
Method: EM (single particle) / Resolution: 2.76 Å

Source
  • poliovirus 3
KeywordsVIRUS LIKE PARTICLE / Poliovirus type 3 / virus-like particles / stabilized state / expanded state

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