Safety and Transcriptome Analysis of Brucella Live Attenuated Vaccine Strain S2 on Cynomolgus Monkeys

Brucellosis, caused by Brucella spp, is an important zoonotic disease leading to enormous economic losses in livestock and posing great threat to public health worldwide. The live attenuated Brucella suis (B. suis) strain S2 is a safe and effective vaccine, and it is most widely used in animals in China. However, S2 vaccination in animals may raise debates and concerns in terms of safety to primates, particularly human. In this study, using cynomolgus monkey as an animal model, we evaluated the safety of the S2 vaccine strain on primate, in addition, we performed transcriptome analysis to determine gene expression profiling on cynomolgus monkeys immunized with the S2 vaccine. Our results suggested that the S2 vaccine was safe to cynomolgus monkeys. Transcriptome analysis identified 663 differentially expressed genes (DEGs), of which 348 were significantly up-regulated and 315 were remarkably down-regulated. Gene Ontology (GO) classification and KEGG pathway analysis indicated that these DEGs were involved in various biological processes, including chemokine signaling pathway, actin cytoskeleton regulation, defense response, immune system processing, and type I interferon signaling pathway. The molecular functions of the DEGs mainly comprised of 2'-5'-oligoadenylate synthetase activity, double-stranded RNA binding and actin binding. Moreover, the cellular components of these DEGs included integrin complex, myosin II complex and blood microparticle. Our findings alleviate the concerns in safety of the S2 vaccine on primates and provide genetic basis of mammalian host response and gene regulation after vaccination with the S2 vaccine. mRNA profile of 4 cynomolgus monkeys immunized with Brucella live vaccine S2 strain and 2 cynomolgus monkeys injected with PBS

布鲁氏菌病（Brucellosis）是由布鲁氏菌属（Brucella spp.）引发的重要人畜共患病，在全球范围内给畜牧业造成巨额经济损失，同时对公共卫生构成严峻威胁。活减毒猪布鲁氏菌（Brucella suis, B. suis）S2株是一款安全有效的疫苗，也是我国目前应用最为广泛的动物用布鲁氏菌疫苗。然而，动物接种S2疫苗可能引发关于灵长类尤其是人类的安全性争议与担忧。本研究以食蟹猴（cynomolgus monkey）作为动物模型，评估了S2疫苗株对灵长类的安全性；此外还对接种S2疫苗的食蟹猴开展转录组分析，以解析其基因表达谱。研究结果显示，S2疫苗对食蟹猴具有良好安全性。转录组分析共鉴定出663个差异表达基因（differentially expressed genes, DEGs），其中348个显著上调，315个显著下调。基因本体（Gene Ontology, GO）分类与京都基因与基因组百科全书（KEGG）通路分析表明，这些差异表达基因参与多种生物学过程，包括趋化因子信号通路、肌动蛋白细胞骨架调控、防御反应、免疫系统加工以及I型干扰素信号通路。差异表达基因的分子功能主要涵盖2'-5'-寡腺苷酸合成酶活性、双链RNA结合活性与肌动蛋白结合活性。此外，这些基因对应的细胞组分包含整合素复合体、肌球蛋白II复合体以及血液微粒。本研究结果缓解了学界对S2疫苗灵长类安全性的担忧，并为阐明S2疫苗接种后哺乳动物宿主应答及基因调控机制提供了遗传学基础。本数据集包含4株接种布鲁氏菌活疫苗S2株的食蟹猴与2株注射磷酸盐缓冲液（PBS）的食蟹猴的mRNA表达谱。