基因工程杂交酵母艾滋病疫苗研究  

Study on hybridized yeast-based HIV vaccine

作　　者：张少恩 熊茜 唐海兵 刘俊云 吴园园 吴道贫 田文志 陆家海[2] 郑伯建[3] 孙娟 

机构地区：[1]深圳市奥克生物技术有限公司,518057 [2]中山大学公共卫生学院 [3]香港大学医学院微生物系

出　　处：《中华微生物学和免疫学杂志》2006年第11期1033-1037,共5页Chinese Journal of Microbiology and Immunology

摘　　要：目的对以酵母为载体所制得的艾滋病候选疫苗进行研究。方法构建表达Gag及IL-2的质粒载体,将表达载体分别转化入酵母细胞,通过酵母杂交获得同时表达两种基因的酵母杂交体,放大培养后经灭活、分装、冻干,制得细胞干粉作为试验的疫苗。用小鼠及食蟹猴对试验疫苗进行有效性及安全性研究。结果杂交酵母可以稳定表达Gag及IL-2；经皮下注射可以分别在小鼠及食蟹猴体内诱导一定水平的细胞免疫反应；对小鼠肿瘤模型的研究表明,疫苗可以诱导有效的免疫保护反应；疫苗的安全性良好,没有明显的毒副作用,只在注射部位引起轻微的红肿,个别动物有低热反应,但均在一周左右恢复正常。结论杂交酵母艾滋病疫苗具有诱导细胞免疫反应的能力；杂交酵母载体疫苗在相关疾病的治疗方面有良好的应用前景。Objective To perform pre-clinical study on a yeast-based HIV vaccine. Methods Plasmids expressing Gag and IL-2 was respectively constructed and then transformed into yeast; yeast hybridization was performed to obtain yeast hybrid concurrently expressing Gag and IL-2; culture of yeast hybrid in large scale was performed. The final vaccine product was obtained through series of process including inactivation, lyophilization and filling. The efficacy and safety of the vaccine was analyzed in mouse and macaque models. Results Expression of Gag and IL-2 in yeast hybrid is stable. Upon subcutaneous injection, HIV vaccine derived from the yeast hybrid could elicit strong Gag-specific cellular immune responses in mice and in macaque models, respectively. In addition, vaccine could also elicit strong protection from tumor challenge in mice. Study on safety indicated that, except for slight tenderness and swelling at the site of injection, there was no obvious acute as well as chronic toxicity. Conclusion Yeast hybrid can he used as a vehicle for vaccine; yeast hybrid-based vaccine is capable of inducing strong antigen-specific cellular immune responses. Our studies imply that yeast hybrid is a promising vector and delivery system for the develolanent of novel therapeutic vaccine candidates against infections and tumors.

关 键 词：基因工程 酵母杂交 HIV 疫苗 

分 类 号：R392[医药卫生—免疫学]