Zhang Weibing, Wang Lei, Chu Liyu, Ma Xu, Gao Wenjing, Wu Yarong, Qiao Yongfeng, Wang Xianjun, Zhao Lu, Hu Hong, Li Xiaoyu, Zhang Ding, Song Tao, Yu Guocan, Wang Haidong, Dong Chunbo, Liu Zhida
College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.
Shanxi Academy of Advanced Research and Innovation, Taiyuan, China.
Front Immunol. 2025 Mar 31;16:1562865. doi: 10.3389/fimmu.2025.1562865. eCollection 2025.
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 circRNA and circRNA 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.
猪流行性腹泻病毒(PEDV)和传染性胃肠炎病毒(TGEV)对新生仔猪构成重大威胁,可导致严重腹泻并可能产生致命后果。除了实施严格的生物安全措施外,有效且安全的疫苗接种对于减轻这些疾病的影响至关重要。在本研究中,PEDV S1(PS1)和TGEV S1(TS1)抗原最初被选为环状RNA疫苗开发的候选抗原。鉴于PS1抗原与TS1抗原相比免疫原性较低,我们策略性地将PS1与猪可结晶片段(Fc)区域偶联以形成PS1F。尽管如此,使用等量的环状RNA和环状RNA混合物制备的二价环状RNA疫苗仍导致针对PS1的抗体水平降低。随后对这两种环状RNA疫苗进行剂量优化,可诱导产生相当水平的抗原特异性抗体和T细胞免疫。此外,二价环状RNA疫苗与商业灭活疫苗(IAV)的序贯接种方案可引发主要由Th1驱动的抗体反应,并有效中和PEDV和TGEV。我们的研究结果不仅为开发基于环状RNA/信使核糖核酸的二价或多价疫苗提供了潜在策略,还突出了序贯接种策略在养猪业中的应用前景。