Frontiers in Microbiology (Oct 2023)
Construction of pseudorabies virus variant attenuated vaccine: codon deoptimization of US3 and UL56 genes based on PRV gE/TK deletion strain
- Mengwei Xu,
- Mengwei Xu,
- Mengwei Xu,
- Mengwei Xu,
- Laixu Zhu,
- Laixu Zhu,
- Laixu Zhu,
- Laixu Zhu,
- Aimin Ge,
- Yamei Liu,
- Yamei Liu,
- Yamei Liu,
- Saisai Chen,
- Saisai Chen,
- Saisai Chen,
- Ziwen Wei,
- Ziwen Wei,
- Ziwen Wei,
- Yating Zheng,
- Yating Zheng,
- Yating Zheng,
- Ling Tong,
- Ling Tong,
- Ling Tong,
- Zhisheng Wang,
- Zhisheng Wang,
- Zhisheng Wang,
- Rongmei Fei,
- Jichun Wang,
- Jichun Wang,
- Jichun Wang,
- Chuanjian Zhang,
- Chuanjian Zhang,
- Chuanjian Zhang
Affiliations
- Mengwei Xu
- National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of the Ministry of Science and Technology, Institute of Veterinary Immunology and Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing, China
- Mengwei Xu
- GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou, China
- Mengwei Xu
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
- Mengwei Xu
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
- Laixu Zhu
- National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of the Ministry of Science and Technology, Institute of Veterinary Immunology and Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing, China
- Laixu Zhu
- GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou, China
- Laixu Zhu
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
- Laixu Zhu
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
- Aimin Ge
- Shandong Vocational Animal Science and Veterinary College, Weifang, China
- Yamei Liu
- National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of the Ministry of Science and Technology, Institute of Veterinary Immunology and Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing, China
- Yamei Liu
- GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou, China
- Yamei Liu
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
- Saisai Chen
- National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of the Ministry of Science and Technology, Institute of Veterinary Immunology and Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing, China
- Saisai Chen
- GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou, China
- Saisai Chen
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
- Ziwen Wei
- National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of the Ministry of Science and Technology, Institute of Veterinary Immunology and Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing, China
- Ziwen Wei
- GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou, China
- Ziwen Wei
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
- Yating Zheng
- National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of the Ministry of Science and Technology, Institute of Veterinary Immunology and Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing, China
- Yating Zheng
- GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou, China
- Yating Zheng
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
- Ling Tong
- National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of the Ministry of Science and Technology, Institute of Veterinary Immunology and Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing, China
- Ling Tong
- GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou, China
- Ling Tong
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
- Zhisheng Wang
- National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of the Ministry of Science and Technology, Institute of Veterinary Immunology and Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing, China
- Zhisheng Wang
- GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou, China
- Zhisheng Wang
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
- Rongmei Fei
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
- Jichun Wang
- National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of the Ministry of Science and Technology, Institute of Veterinary Immunology and Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing, China
- Jichun Wang
- GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou, China
- Jichun Wang
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
- Chuanjian Zhang
- National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of the Ministry of Science and Technology, Institute of Veterinary Immunology and Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing, China
- Chuanjian Zhang
- GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou, China
- Chuanjian Zhang
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
- DOI
- https://doi.org/10.3389/fmicb.2023.1248573
- Journal volume & issue
-
Vol. 14
Abstract
Since 2011, pseudorabies based on the pseudorabies virus (PRV) variant has emerged as a serious health issue in pig farms in China. The PRV gE/TK or gE/gI/TK deletion strains protect against emerging PRV variants. However, these variants may cause lethal infections in newborn piglets without PRV antibodies. Previous studies have shown that codon deoptimization of a virulence gene causes virus attenuation. Accordingly, we deoptimized US3-S (US3 gene encoding a short isoform that represents approximately 95% of the total US3 transcription) and UL56 genes (first 10 or all codons) of PRV gE/TK deletion strain (PRVΔTK&gE−AH02) to generate six recombinant PRVs through bacterial artificial chromosome technology. In swine testicular cells, recombinant PRVs with all codon deoptimization of US3-S or UL56 genes were grown to lower titers than the parental virus. Notably, US3-S or UL56 with all codon deoptimization reduced mRNA and protein expressions. Subsequently, the safety and immunogenicity of recombinant PRVs with codon deoptimization of US3-S or UL56 are evaluated as vaccine candidates in mice and piglets. The mice inoculated with recombinant PRVs with codon deoptimization of US3-S or UL56 showed exceptional survival ability without severe clinical signs. All codons deoptimized (US3-S and UL56) significantly decreased virus load and attenuated pathological changes in the brains of the mice. Moreover, the protection efficiency offered by recombinant PRVs with codon deoptimization of US3-S or UL56 showed similar effects to PRVΔTK&gE−AH02. Remarkably, the 1-day-old PRV antibody-negative piglets inoculated with PRVΔTK&gE-US3-ST−CD (a recombinant PRV with all codon deoptimization of US3-S) presented no abnormal clinical symptoms, including fever. The piglets inoculated with PRVΔTK&gE-US3-ST−CD showed a high serum neutralization index against the PRV variant. In conclusion, these results suggest using codon deoptimization to generate innovative live attenuated PRV vaccine candidates.
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