Qing Ying, Liu Jiawen, Huang Xiaobo, Li Yaqing, Zhang Yudi, Chen Jie, Wen Xintian, Cao Sanjie, Wen Yiping, Wu Rui, Yan Qigui, Ma Xiaoping
Research Center of Swine Disease, Infectious Disease and Microarray, College of Veterinary Medicine, Sichuan Agricultural University, Huimin Road 211, Wenjiang District, Chengdu, 611130, China.
Sichuan Key Laboratory of Conservation Biology for Endangered Wild Life, Chengdu Research Base of Giant Panda Breeding, Chengdu, China.
Virus Genes. 2016 Apr;52(2):218-27. doi: 10.1007/s11262-016-1296-z. Epub 2016 Feb 2.
Attenuated Salmonella typhimurium (S. typhimurium) was selected as a transgenic vehicle for the development of live mucosal vaccines against transmissible gastroenteritis virus (TGEV) based on the M gene. An approximate 1.0 kb DNA fragment, encoding for glycoprotein M, was amplified by RT-PCR and cloned into eukaryotic expression vector pVAX1. The recombinant plasmid pVAX-M was transformed by electroporation into attenuated S. typhimurium SL7207, and the expression and translation of the pVAX-M delivered by recombinant S. typhimurium SL7207 (pVAX-M) was detected both in vitro and in vivo. BALB/c mice were inoculated orally with SL7207 (pVAX-M) at different dosages to evaluate safety of the vaccines. The bacterium was safe to mice at a dosage of 2 × 10(9) CFU, almost eliminated from the spleen and liver at week 4 post-immunization and eventually cleared at week 6. Mice immunized with 1 × 10(9) CFU of SL7207 (pVAX-M) elicited specific anti-TGEV local mucosal and humoral responses including levels of IgA, IgG, IL-4, and IFN-γ as measured by indirect ELISA assay. Moreover, the control groups (pVAX group, PBS group) maintained at a normal level during week 4-8 post-immunization. The results indicated that attenuated S. typhimurium could be used as a delivery vector for oral immunization of TGEV M gene vaccine.
减毒鼠伤寒沙门氏菌被选作一种转基因载体,用于研发基于M基因的抗传染性胃肠炎病毒(TGEV)的活黏膜疫苗。通过逆转录聚合酶链反应(RT-PCR)扩增出一段约1.0 kb编码糖蛋白M的DNA片段,并克隆到真核表达载体pVAX1中。重组质粒pVAX-M通过电穿孔法转化到减毒鼠伤寒沙门氏菌SL7207中,检测重组鼠伤寒沙门氏菌SL7207(pVAX-M)递送的pVAX-M在体外和体内的表达及翻译情况。用不同剂量的SL7207(pVAX-M)经口接种BALB/c小鼠,以评估疫苗的安全性。该菌在剂量为2×10⁹CFU时对小鼠是安全的,免疫后第4周几乎从脾脏和肝脏中清除,最终在第6周清除。用1×10⁹CFU的SL7207(pVAX-M)免疫的小鼠引发了特异性抗TGEV局部黏膜和体液免疫反应,包括通过间接酶联免疫吸附测定法测得的IgA、IgG、IL-4和IFN-γ水平。此外,对照组(pVAX组、PBS组)在免疫后第4至8周维持在正常水平。结果表明,减毒鼠伤寒沙门氏菌可作为TGEV M基因疫苗口服免疫的递送载体。