A VSV-based oral rabies vaccine was sentineled by Peyer's patches and induced a timely and durable immune response

文献类型： 外文期刊

第一作者： Wang, Shen

作者： Wang, Shen;Wang, Zhenshan;Wang, Weiqi;Sun, Hongyu;Feng, Na;Zhao, Yongkun;Wang, Tiecheng;Xia, Xianzhu;Yan, Feihu;Wang, Zhenshan;Sun, Hongyu;Wang, Jianzhong;Wang, Weiqi;Xia, Xianzhu

作者机构：

期刊名称：MOLECULAR THERAPY （ 影响因子：12.0； 五年影响因子：12.4 ）

ISSN： 1525-0016

年卷期： 2025 年 33 卷 4 期

页码：

收录情况： SCI

摘要： The global eradication of canine-mediated human rabies remains an ongoing public health priority. While conventional oral rabies vaccines (ORVs) have demonstrated partial success in interrupting zoonotic transmission, current formulations necessitate improvements in both immunogenic profiles and mechanistic clarity. Herein, we present a recombinant vesicular ERA-G) engineered to express the glycoprotein of the rabies virus (RABV) ERA strain, substituting the native VSV glycoprotein. Preclinical evaluation across multiple mammalian species pus, and Nyctereutes procyonoides) revealed rapid seroconversion and sustained neutralizing antibody responses. Challenge experiments demonstrated 100% survival efficacy in pre-exposure prophylaxis models, with partial protection observed in post-exposure scenarios. Safety assessments confirmed significant attenuation of neurotropism and absence of horizontal transmission or environmental shedding. Furthermore, evidence showed that rVSVDG-ERA-G is recognized by Peyer's patches (PPs), where a cascade activation of immune cells occurred. From another perspective, the absence of functional microfold cells in PPs hampered the initiation and progression of immune responses. This proof-of-concept study establishes rVSVDG-ERA-G as an ORV candidate with enhanced biosafety and cross-species immunogenicity. The elucidation of M celldependent mucosal priming mechanisms provides a rational framework for optimizing the targeted delivery of ORVs.

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