甲磺酸去铁胺佐剂对甲型肝炎病毒抗原诱导小鼠体液免疫应答的影响

Effect of deferoxamine adjuvant on humoral immune response induced by hepatitis A virus antigen in mice

目的探讨甲磺酸去铁胺（deferoxamine，DFO）佐剂对甲型肝炎病毒（hepatitis A virus antigen，HAV）抗原诱导小鼠体液免疫应答的影响。方法将不同剂量的DFO（0.6、1、4、8mg）佐剂分别与HAV抗原18EU混合，免疫ICR小鼠，并设生理盐水对照组（生理盐水200 μl）、HAV抗原对照组（HAV 18 EU）、铝佐剂对照组（铝佐剂300μg＋HAY抗原18EU）和复合佐剂组（HAY抗原18EU＋DFO1mg＋铝佐剂150 μg），均经腹部皮下多点注射，0.2ml／只，共免疫1次。分别于免疫后第4、8、12、16周，采用间接ELISA法检测小鼠血清中抗-HAV IgG水平，并进行安全性试验。结果除生理盐水对照组外，其他各组小鼠血清在各时间点均能检测到抗.HAVIgG；除DFO 0.6mg组外，抗体滴度均在第8周达峰值；不同剂量DFO组的抗体水平均明显高于HAV抗原对照组，其中DFO4mg和8mg组在8～16周时抗体水平显著高于HAV抗原对照组，且差异有统计学意义（P〈0.05），但与铝佐剂对照组比较，差异无统计学意义（P〉0.05）；在8～16周时，同一时间DFO4mg、DFO8mg和复合佐剂组的抗体水平较高，并能维持较长时间，至第16周时仍能达到与铝佐剂对照组相当的水平。结论DFO佐剂能显著增强HAV抗原诱导小鼠的体液免疫应答，有望开发为一种可替代铝佐剂的新型佐剂。

Objective To investigate the effect of deferoxamine （DFO） on humoral immune response induced by hepatitis A virus （HAV） antigen in mice. Methods ICR mice were immunized with 18 EU HAV antigen combined with DFO at various dosages （0. 6, 1, 4 and 8 mg） respectively by s. c. injection in several sites at a volume of 0. 2 ml, using 200 μl of physiological saline, 18 EU HAV antigen alone and 300 μg aluminum adjuvant ＋ 18 EU HAV antigen and complex adjuvant （18 EU HAV antigen ＋ 1 mg DFO ＋ 150 μg aluminum adjuvant） as controls. Serum samples were collected at weeks 4, 8, 12 and 16 after immunization, and determined for anti-HAV IgG levels by indirect ELISA. Meanwhile, safety test was performed. Results Anti-HAV IgGs were detected in sera of mice at various time points in various groups except physiological saline control group. The IgG titers in various groups except DFO 0.6 mg group reached peak values at weeks 8 after immu- nization. The anti-HAV IgG levels of mice after immunization with HAV antigen combined with DFO adjuvant at various dosages were higher, of which those in DFO 4 and 8 mg groups at weeks 8 ～ 16 were significantly higher, than that in HAV antigen control group （P 〈0.05 ）, which showed no significant difference with that in aluminum adjuvant control group （P 〈0.05）. The IgG levels in DFO 4 mg, DFO 8 mg and complex adjuvant control groups at the same time points at weeks 8 ～ 16 were relatively high and persistent, which were equal to that in aluminum adjuvant control group until week 16. Conclusion DFO enhanced the humoral immune response induced by HAV in mice significantly, which might be developed as a novel adjuvant instead of aluminum adjuvant.