免疫佐剂对不同剂量丙肝核酸疫苗效果的影响  

Effects of Distinct Adjuvant on HCV DNA Vaccine at Different Dosages

作　　者：金博[1] Richard Y.-H.Wang 程留芳[1] 裘奇[2] 史维国[2] 

机构地区：[1]中国解放军总医院消化内科,北京市100853 [2]国立卫生研究院,活伦麦哥纽荪临床中心,输血医学部传染病组

出　　处：《世界华人消化杂志》2005年第12期1429-1433,共5页World Chinese Journal of Digestology

摘　　要：目的:观察不同佐剂对不同剂量HCVDNA疫苗效果的影响.方法:雌性Balb/c小鼠分别用脂质体DDAB/EPC和氢氧化铝为佐剂的HCVDNA疫苗(由HCV结构基因、NS3和NS5b各50μg或100μg等量混合)免疫3次,ELISPOT法观察脾淋巴细胞受HCV核心、E2、E1/E2、NS3和NS5b蛋白刺激后细胞因子的产生.结果:DDAB/EPC纽产生IFN-γ和IL-4较多,用核心、E2或E1/E2刺激,显著高于裸DNA和氢氧化铝组(P<0.05).以氢氧化铝为佐剂用每种DNA100μg剂量免疫的小鼠,在受抗原刺激后,除E2外,其脾淋巴细胞产生IL-4的能力显著高于相应裸DNA组(P<0.05).在多数情况下,接受每种DNA10μg剂量的小鼠产生IFN-γ和IL-4的能力显著高于接种每种50μg者(P<0.05).与裸DNA组及DDAB/EPC组比较,氢氧化铝组小鼠淋巴细胞产生的IL-4多于IFN—γ.结论:DDAB/EPC对HCVDNA疫苗有很强的免疫佐剂效应,氢氧化铝是Th2佐剂,可将DNA疫苗Th1为主的免疫特性转换为以Th2为主,50μg的HCVDNA疫苗似不能诱导小鼠产生有效的免疫反应.AIM: To explore the effects of different adjuvants on different dosages of hepatitis C virus (HCV) DNA vaccine. METHODS: Female Balb/c mice were primed by HCV DNA vaccine composed of HCV structure gene DNA, HCV nonstructure gene 3 (NS3) and NS5b at the dosages of either 100 μlg/each or 50μg/each with liposome DDAB/EPC or aluminum hydroxide and boosted twice accordingly. The cytokine profiles induced by various HCV antigens on splenocytes from the immunized mice were assessed by ELISPOT assay using in vitro splenocyte culture stimulated with recombinant HCV core, E2, E1/ E2, NS3 or NS5b protein. RESULTS: The frequency of IFN-γor IL-4 secreting cells found in splenocytes stimulated with HCV core, E2, or E1/ E2 from the mice vaccinated with HCV recombinant DNA in DDAB/EPC adjuvant was significantly higher (P<0.05) than that from mice immunized with either naked DNA or DNA formulated in aluminum hydroxide. The frequency of IL-4 secreting cells from mice immunized with HCV DNA at a dosage of 100 μg/each mixed with aluminum hy- droxide was significantly higher than that from naked DNA when the splenocytes were stimulated with all the antigens tested except E2 (P<0.05). At many cases, lymphocytes from mice received 100 μg/each DNA have more IFN-γor IL-4 productions compared with those from mice with 50 μg/each (P<0.05). The lymphocytes from mice primed and boosted with HCV DNA plus aluminum hydroxide can produce more IL-4 than IFN-γin contrast with the cytokine profile of mice immunized with naked DNA or DDAB/EPC adjuvant. CONCLUSION: Liposome DDAB/EPC has strong adjuvant effects on HCV DNA vaccine. Aluminum hydroxide is a Th2 adjuvant and can convert the Th1 nature of DNA vaccine to Th2-biased immunity. It seems that the dosage of 50 μg of HCV DNA vaccine is not adequate to elicit efficient immunity in mice.

关 键 词：免疫佐剂 丙肝核酸疫苗 氢氧化铝 丙型肝炎病毒 

分 类 号：R392[医药卫生—免疫学]