中国兽医科学2025，Vol.55Issue(10)：1299-1309,11.DOI:10.16656/j.issn.1673-4696.2025.0159
表达纤突蛋白的重组水疱性口炎病毒在转hACE2基因小鼠中的安全性和免疫原性研究
Evaluation of safety and immunogenicity of recombinant vesicular stomatitis virus expressing spike protein in hACE2 transgenic mice
摘要
Abstract
In the study,the codon-optimized SARS-CoV-2 spike(S)protein gene or its mutant with 986 lysine and 987 valine to proline(S2P)were cloned into the highly attenuated VSVMTvector,respectively.Replicative and nonreplicative recombinant virus rVSV-S2P and rVSV-S2P were constructed after trans-fected into BHK21 cells.Besides,the replication-incompetent rVSVMT-S2P can infect cells that do not express hACE2 but cannot be continuously passaged,while the replication-competent rVSVMT-S can be con-tinuously passaged in cells expressing hACE2.Animal safety trials indicated that the rVSVMT viruses are safe in both healthy and immunocompromised hACE2 transgenic mice,and did not cause body weight loss,abnormal blood routine indicators,residual virus in tissues,or increase of proinflammatory cy-tokines.Animal immunogenicity tests showed that rVSVMT recombinant virus expressing S protein antigen can induce a comprehensive immune response(humoral immunity,mucosal immunity,cellular immunity)in healthy hACE2 transgenic mice,while the immune response is relatively weakened in immunocompromised hACE2 transgenic mice.This study is expected to provide a new strategy for the development of novel mu-cosal vaccine delivery vectors.关键词
水泡性口炎病毒/黏膜疫苗/hACE2转基因小鼠Key words
vesicular stomatitis virus/mucosal vaccine/hACE2 transgenic mice分类
农业科技引用本文复制引用
张恩,肖贤,孙涛..表达纤突蛋白的重组水疱性口炎病毒在转hACE2基因小鼠中的安全性和免疫原性研究[J].中国兽医科学,2025,55(10):1299-1309,11.基金项目
上海市2022年度"科技创新行动计划"生物医药科技支撑专项(以假型化VSV为载体研制新冠病毒δ变异株应急免疫疫苗,22S11902200) （以假型化VSV为载体研制新冠病毒δ变异株应急免疫疫苗,22S11902200）
