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TitleStructural insight into the assembly and D antigenicity of polio type 1 stabilized virus-like particles.
Journal, issue, pagesNPJ Vaccines, Year 2026
Publish dateFeb 24, 2026
AuthorsQin Hong / Tian Chen / Wenyu Han / Shuxia Wang / Chaoyang Lian / Yujie Zhang / Lizhu Ruan / Tingfeng Wang / Cheng Lin / Congcong Song / Qingwei Liu / Xiaoli Wang / Yao Cong / Zhong Huang /
PubMed AbstractThe inherent instability of poliovirus capsids presents a formidable challenge for developing next-generation vaccines suitable for a post-eradication world. Here, we address this by engineering a ...The inherent instability of poliovirus capsids presents a formidable challenge for developing next-generation vaccines suitable for a post-eradication world. Here, we address this by engineering a thermally stabilized virus-like particle (sVLP) derived from the poliovirus serotype 1 (PV1) Mahoney-SC7 mutant and elucidating its atomic-level structure. Produced at remarkably high yields in Pichia pastoris yeast, our engineered sVLP maintains a native, D-antigenic conformation and elicits a potent neutralizing antibody response in mice, in sharp contrast to unstable wild-type VLP (wtVLP) which adopts an expanded, non-immunogenic form. Our 2.43 Å resolution cryo-EM structure reveals precisely how seven stabilizing mutations cooperatively enhance inter-protomer contacts and rigidify surface loops to lock the particle in its immunogenic state. We further define a critical D-antigenic epitope by determining the 2.60 Å structure of the sVLP in complex with a novel D-antigen-specific, neutralizing monoclonal antibody, 3G10, elucidating the structural mechanisms of D-antigen recognition and virus neutralization by 3G10. These findings provide a definitive structural blueprint for engineering stable, immunogenic vaccines for PVs and other enteroviruses and also deliver a vital reagent for ensuring vaccine quality control.
External linksNPJ Vaccines / PubMed:41735326
MethodsEM (single particle)
Resolution2.43 - 2.95 Å
Structure data

65817

9wag

EMDB-65817, PDB-9wag:
Yeast-expressed polio type 1 expanded virus-like particles
Method: EM (single particle) / Resolution: 2.95 Å

65818

9wah

EMDB-65818, PDB-9wah:
Yeast-expressed polio type 1 stabilized virus-like particles
Method: EM (single particle) / Resolution: 2.43 Å

65819

9wai

EMDB-65819, PDB-9wai:
Yeast-expressed polio type 1 stablized virus-like particles with 3G10 Fab
Method: EM (single particle) / Resolution: 2.6 Å

Source
  • Homo sapiens (human)
  • poliovirus 1
  • mus musculus (house mouse)
KeywordsVIRUS LIKE PARTICLE / Poliovirus type 1 / virus-like particles / expanded state / VIRAL PROTEIN / compact state / VIRUS LIKE PARTICLE/IMMUNE SYSTEM / antibody / VIRUS LIKE PARTICLE-IMMUNE SYSTEM complex

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