Bivalent circular RNA vaccines against porcine epidemic diarrhea virus and transmissible gastroenteritis virus

Porcine Epidemic Diarrhea Virus (PEDV) and Transmissible Gastroenteritis Virus (TGEV) pose significant threats to neonatal piglets, leading to severe diarrhea and potentially lethal consequences. Beyond enforcing stringent biosecurity protocols, effective and safe vaccinations are crucial in mitigat...

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Main Authors: Weibing Zhang, Lei Wang, Liyu Chu, Xu Ma, Wenjing Gao, Yarong Wu, Yongfeng Qiao, Xianjun Wang, Lu Zhao, Hong Hu, Xiaoyu Li, Ding Zhang, Tao Song, Guocan Yu, Haidong Wang, Chunbo Dong, Zhida Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1562865/full
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author Weibing Zhang
Weibing Zhang
Lei Wang
Lei Wang
Liyu Chu
Xu Ma
Xu Ma
Wenjing Gao
Wenjing Gao
Yarong Wu
Yongfeng Qiao
Yongfeng Qiao
Xianjun Wang
Xianjun Wang
Lu Zhao
Lu Zhao
Hong Hu
Hong Hu
Xiaoyu Li
Ding Zhang
Tao Song
Guocan Yu
Haidong Wang
Chunbo Dong
Chunbo Dong
Zhida Liu
Zhida Liu
author_facet Weibing Zhang
Weibing Zhang
Lei Wang
Lei Wang
Liyu Chu
Xu Ma
Xu Ma
Wenjing Gao
Wenjing Gao
Yarong Wu
Yongfeng Qiao
Yongfeng Qiao
Xianjun Wang
Xianjun Wang
Lu Zhao
Lu Zhao
Hong Hu
Hong Hu
Xiaoyu Li
Ding Zhang
Tao Song
Guocan Yu
Haidong Wang
Chunbo Dong
Chunbo Dong
Zhida Liu
Zhida Liu
author_sort Weibing Zhang
collection DOAJ
description Porcine Epidemic Diarrhea Virus (PEDV) and Transmissible Gastroenteritis Virus (TGEV) pose significant threats to neonatal piglets, leading to severe diarrhea and potentially lethal consequences. Beyond enforcing stringent biosecurity protocols, effective and safe vaccinations are crucial in mitigating the impact of these diseases. In this study, the PEDV S1 (PS1) and TGEV S1 (TS1) antigens were initially chosen as candidates for the development of circRNA vaccines. Recognizing the comparatively lower immunogenicity of the PS1 antigen in contrast to the TS1 antigen, we strategically conjugated the PS1 with the pig fragment crystallizable (Fc) region to form PS1F. Despite these efforts, the bivalent circRNA vaccine prepared using an equal amount of the circRNAPS1F and circRNATS1 mixture still led to a reduction in the antibody levels against PS1. Subsequent dosage optimization of these two circRNA vaccines resulted in the induction of comparable levels of antigen specific antibodies and T cell immunity. Furthermore, sequential vaccination regimen with bivalent circRNA vaccine and commercial inactivated vaccines (IAV) could elicit a predominantly Th1-driven antibody responses and effectively neutralize both PEDV and TGEV. Our findings not only provide a potential strategy for the development of bivalent or multivalent circRNA/mRNA-based vaccines but also highlight the promising application of sequential vaccination strategies within the swine industry.
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spelling doaj-art-feaf4f81c22c4423a27ad6d1ee06a91f2025-08-20T02:10:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15628651562865Bivalent circular RNA vaccines against porcine epidemic diarrhea virus and transmissible gastroenteritis virusWeibing Zhang0Weibing Zhang1Lei Wang2Lei Wang3Liyu Chu4Xu Ma5Xu Ma6Wenjing Gao7Wenjing Gao8Yarong Wu9Yongfeng Qiao10Yongfeng Qiao11Xianjun Wang12Xianjun Wang13Lu Zhao14Lu Zhao15Hong Hu16Hong Hu17Xiaoyu Li18Ding Zhang19Tao Song20Guocan Yu21Haidong Wang22Chunbo Dong23Chunbo Dong24Zhida Liu25Zhida Liu26College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Shanxi Medical University, Taiyuan, ChinaHebei Key Laboratory of Preventive Veterinary, College of Animal Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan, ChinaAnkerui (Shanxi) Biological Cell Co., Ltd., Taiyuan, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, ChinaHebei Key Laboratory of Preventive Veterinary, College of Animal Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao, ChinaKey Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan, ChinaPorcine Epidemic Diarrhea Virus (PEDV) and Transmissible Gastroenteritis Virus (TGEV) pose significant threats to neonatal piglets, leading to severe diarrhea and potentially lethal consequences. Beyond enforcing stringent biosecurity protocols, effective and safe vaccinations are crucial in mitigating the impact of these diseases. In this study, the PEDV S1 (PS1) and TGEV S1 (TS1) antigens were initially chosen as candidates for the development of circRNA vaccines. Recognizing the comparatively lower immunogenicity of the PS1 antigen in contrast to the TS1 antigen, we strategically conjugated the PS1 with the pig fragment crystallizable (Fc) region to form PS1F. Despite these efforts, the bivalent circRNA vaccine prepared using an equal amount of the circRNAPS1F and circRNATS1 mixture still led to a reduction in the antibody levels against PS1. Subsequent dosage optimization of these two circRNA vaccines resulted in the induction of comparable levels of antigen specific antibodies and T cell immunity. Furthermore, sequential vaccination regimen with bivalent circRNA vaccine and commercial inactivated vaccines (IAV) could elicit a predominantly Th1-driven antibody responses and effectively neutralize both PEDV and TGEV. Our findings not only provide a potential strategy for the development of bivalent or multivalent circRNA/mRNA-based vaccines but also highlight the promising application of sequential vaccination strategies within the swine industry.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1562865/fullcircRNA vaccinebivalentporcine epidemic diarrhea virustransmissible gastroenteritis virussequential vaccination
spellingShingle Weibing Zhang
Weibing Zhang
Lei Wang
Lei Wang
Liyu Chu
Xu Ma
Xu Ma
Wenjing Gao
Wenjing Gao
Yarong Wu
Yongfeng Qiao
Yongfeng Qiao
Xianjun Wang
Xianjun Wang
Lu Zhao
Lu Zhao
Hong Hu
Hong Hu
Xiaoyu Li
Ding Zhang
Tao Song
Guocan Yu
Haidong Wang
Chunbo Dong
Chunbo Dong
Zhida Liu
Zhida Liu
Bivalent circular RNA vaccines against porcine epidemic diarrhea virus and transmissible gastroenteritis virus
Frontiers in Immunology
circRNA vaccine
bivalent
porcine epidemic diarrhea virus
transmissible gastroenteritis virus
sequential vaccination
title Bivalent circular RNA vaccines against porcine epidemic diarrhea virus and transmissible gastroenteritis virus
title_full Bivalent circular RNA vaccines against porcine epidemic diarrhea virus and transmissible gastroenteritis virus
title_fullStr Bivalent circular RNA vaccines against porcine epidemic diarrhea virus and transmissible gastroenteritis virus
title_full_unstemmed Bivalent circular RNA vaccines against porcine epidemic diarrhea virus and transmissible gastroenteritis virus
title_short Bivalent circular RNA vaccines against porcine epidemic diarrhea virus and transmissible gastroenteritis virus
title_sort bivalent circular rna vaccines against porcine epidemic diarrhea virus and transmissible gastroenteritis virus
topic circRNA vaccine
bivalent
porcine epidemic diarrhea virus
transmissible gastroenteritis virus
sequential vaccination
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1562865/full
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