Wang Jun, Qin Songkang, Li Kuanhao, Yin Xin, Sun Dongbo, Chang Jitao
State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 5 Xinfeng Road, Sartu District, Daqing 163319, China.
Microorganisms. 2025 Jul 4;13(7):1579. doi: 10.3390/microorganisms13071579.
Mucosal immunization represents a promising strategy for preventing enteric infections. Rotavirus (RV), a leading gastrointestinal pathogen distinguished by its remarkable stability and segmented double-stranded RNA genome, has been engineered into a versatile oral vaccine vector through advanced reverse genetics systems. The clinical efficacy of live-attenuated RV vaccines highlights their unique capacity to concurrently induce mucosal IgA responses and systemic neutralizing antibodies, positioning them as a multiple action vector for multiple immune protection. In this review, we summarize the RV colonization of the intestine and stimulation of intestinal immunity, as well as recent advancements in RV reverse genetics, and focus on their application in the rational design of a multivalent mucosal vaccine vector targeting enteric pathogens considering the advantages and challenges of RV as a vector. We further propose molecular strategies to overcome genetic instability in recombinant RV vectors, including the codon optimization of heterologous inserts. These insights provide a theoretical foundation for developing next-generation mucosal immunization platforms with enhanced safety, stability, and cross-protective efficacy.
黏膜免疫是预防肠道感染的一种有前景的策略。轮状病毒（RV）是一种主要的胃肠道病原体，以其显著的稳定性和分段双链RNA基因组为特征，通过先进的反向遗传学系统已被改造成为一种通用的口服疫苗载体。减毒活RV疫苗的临床疗效突出了它们同时诱导黏膜IgA反应和全身中和抗体的独特能力，使其成为具有多种免疫保护作用的多效性载体。在本综述中，我们总结了RV在肠道中的定植及对肠道免疫的刺激，以及RV反向遗传学的最新进展，并鉴于RV作为载体的优势和挑战，着重探讨其在合理设计针对肠道病原体的多价黏膜疫苗载体中的应用。我们进一步提出克服重组RV载体遗传不稳定性的分子策略，包括对异源插入片段进行密码子优化。这些见解为开发具有更高安全性、稳定性和交叉保护效力的下一代黏膜免疫平台提供了理论基础。
