8ZH6

Yeast-expressed polio type 2 expanded virus-like particles

Summary for 8ZH6

• Entry DOI: 10.2210/pdb8zh6/pdb
• EMDB information: 60095
• Descriptor: VP1, VP3, VP2 (3 entities in total)
• Functional Keywords: poliovirus type 2, virus-like particles, compact state, viral protein
• Biological source: Poliovirus 2; More
• Total number of polymer chains: 3
• Total formula weight: 89580.28

Authors

Hong, Q.,Cong, Y. (deposition date: 2024-05-10, release date: 2024-09-18, Last modification date: 2024-12-25)

Primary citation

Hong, Q.,Wang, S.,Wang, X.,Han, W.,Chen, T.,Liu, Y.,Cheng, F.,Qin, S.,Zhao, S.,Liu, Q.,Cong, Y.,Huang, Z.
Vaccine Potency and Structure of Yeast-Produced Polio Type 2 Stabilized Virus-like Particles.
Vaccines (Basel), 12:-, 2024

PubMed Abstract: Poliovirus (PV) is on the brink of eradication due to global vaccination programs utilizing live-attenuated oral and inactivated polio vaccines. Recombinant PV virus-like particles (VLPs) are emerging as a safe next-generation vaccine candidate for the impending polio-free era. In this study, we investigate the production, antigenicity, thermostability, immunogenicity, and structures of VLPs derived from PV serotype 2 (PV2) wildtype strain and thermally stabilized mutant (wtVLP and sVLP, respectively). Both PV2 wtVLP and sVLP are efficiently produced in yeast. The PV2 sVLP displays higher levels of D-antigen and significantly enhanced thermostability than the wtVLP. Unlike the wtVLP, the sVLP elicits neutralizing antibodies in mice at levels comparable to those induced by inactivated polio vaccine. The addition of an aluminum hydroxide adjuvant to sVLP results in faster induction and a higher magnitude of neutralizing antibodies. Furthermore, our cryo-EM structural study of both sVLP and wtVLP reveals a native conformation for the sVLP and a non-native expanded conformation for the wtVLP. Our work not only validates the yeast-produced PV2 sVLP as a promising vaccine candidate with high production potential but also sheds light on the structural mechanisms that underpin the assembly and immunogenicity of the PV2 sVLP. These findings may expedite the development of sVLP-based PV vaccines.

PubMed: 39340107
DOI: 10.3390/vaccines12091077

Experimental method

ELECTRON MICROSCOPY (3.1 Å)