Optimizing encephalomyocarditis virus VP1 protein assembly on pseudorabies virus envelope via US9 protein anchoring
Live herpesvirus-vectored vaccines are critical in veterinary medicine, but they can sometimes offer insufficient protection due to suboptimal antigen expression or localization. Encephalomyocarditis virus (EMCV) is a significant zoonotic threat, with VP1 protein as a key immunogen on its capsid. To...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
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| Series: | Virulence |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2024.2445235 |
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| Summary: | Live herpesvirus-vectored vaccines are critical in veterinary medicine, but they can sometimes offer insufficient protection due to suboptimal antigen expression or localization. Encephalomyocarditis virus (EMCV) is a significant zoonotic threat, with VP1 protein as a key immunogen on its capsid. To enhance immunogenicity, we explored the use of recombinant pseudorabies virus (rPRV) as a vaccine vector against EMCV. In silico analysis indicated that fusing VP1 with US9 enhances the formation of a type II transmembrane heterodimer. We constructed six rPRV groups expressing different VP1 variants and found that VP1 fused with US9’s C-terminal (US9-VP1) enhances VP1’s membrane localization and its incorporation into the PRV envelope, unlike wild-type VP1. Immunogold electron microscopy illustrated that rPRV with deleted US8 and US9, supplemented with US8 regulatory sequence (rΔ89-U9VP1), improved VP1 incorporation into the viral envelope. Post-immunization, only rΔ89-U9VP1 provided 100% protection against EMCV in mice and induced high levels of virus-neutralizing antibodies in piglets. Additionally, rPRV expressing VP1 stimulated robust T-cell responses, as demonstrated by flow cytometry and ELISpot assays. This study introduces rPRV as a potential EMCV vaccine, demonstrating that the selection of the US9 C-terminal domain and US8 regulatory sequence significantly enhances the presentation of heterologous antigens, improving vaccine efficacy. |
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| ISSN: | 2150-5594 2150-5608 |