疟疾DNA疫苗免疫接种方法对小鼠 体液免疫应答的影响

摘要

Objective To compare humoral immune responses and T helper cellpolarization induced by different injection methods of a multi-epitope chimeric DNA vaccine. Methods The multi-epitope DNA vaccine of Plasmodium falciparum was constructed and inoculated into BALB/c mice by intramuscular, intradermal or gene gun injection. The antibody against either recombinant protein or epitope peptides and the subclass of the antibody was detected by ELISA. Results Specific antibodies were detected in mice serum after the inoculation by all methods above. The antibody titer induced by gene gun injection was 100 times higher than that by intramuscular injection in each unit dose of DNA. IgG1 was predominant in serum of mice immunized by gene gun, while IgG2a was predominant in serum of mice immunized by intramuscular and intradermal injections. There is no difference in epitope specificity by all methods of injection. Conclusions Both antibody level and T helper cell profile were affected by the ways of injection in mice immunized with a DNA vaccine. DNA delivered by gene gun induced highest antibody titer and intramuscular injection induced the lowest one. TH2 profile was induced by DNA-gold particle delivered by gene gun, while TH1 profile was induced by Saline DNA injected by either intramuscular or intradermal route, which means the localization of body did not affect the T helper cell profile.%目的 探讨DNA疫苗免疫接种方法对抗体水平及辅助性T细胞极化的影响。方法 利用DNA重组技术构建恶性疟原虫红内期多表位DNA疫苗，通过基因枪、肌肉注射、皮内注射等接种方法免疫小鼠，经ELISA测定该疫苗诱导产生特异性抗体的总量、亚型及表位特异性，比较不同免疫接种方法对DNA疫苗诱导产生抗体及辅助性T细胞极化的影响。结果 接种DNA疫苗的小鼠经3次免疫后都产生了较高滴度的抗重组蛋白抗体。基因枪组单位DNA诱导抗体滴度是肌注组的120倍。基因枪组小鼠血清抗体以IgG1升高为主，而肌注和皮内注射组小鼠血清抗体均以IgG2a升高为主。各免疫接种组诱导产生的抗表位多肽抗体特异性相同。结论 不同免疫接种方法不但会影响血清总免疫球蛋白水平，还能使辅助性T细胞向不同方向极化。肌注和皮内注射诱导产生以IgG2a为主的TH1型免疫应答，基因枪接种诱导产生以IgG1为主的TH2型免疫应答。DNA疫苗的摄取方式可明显影响辅助性T细胞的极化。