Ad5-HIVgag免疫的食蟹猴中腺病毒中和抗体与Gag特异性细胞免疫反应的研究

目的 观察不同剂量的重组腺病毒疫苗Ad5-HIVgag反复肌内注射免疫食蟹猴后,食蟹猴体内产生的腺病毒中和抗体水平及Gag特异性细胞免疫反应水平,初步探讨腺病毒中和抗体的产生对Gag特异性细胞免疫反应的影响.方法 将24只食蟹猴随机分为4组：对照组、低剂量组、中剂量组、高剂量组.每3周免疫1次,连续免疫5次.免疫前及免疫后不同时间点用中和实验检测动物体内腺病毒中和抗体水平,用Elispot方法检测Gag特异性细胞免疫反应水平.结果 初次免疫后3周3个实验组动物都检测到了较高水平的腺病毒中和抗体,在初次免疫后8周达到高峰,恢复期结束时略有下降.初次免疫后5周三个实验组动物都检测到了Gag特异性细胞免疫反应,除初次免疫后12周反应水平有所下降,其他时间点细胞反应呈逐渐增高趋势,但各剂量组间未见明显的量效关系.结论 在一定的剂量范围内反复多次应用Ad5-HIVgag免疫食蟹猴后,可产生针对腺病毒的中和抗体,随着免疫次数的增多Gag特异性细胞免疫反应有增高趋势,Ad5疫苗免疫后中和抗体的产生对Ad5疫苗反复应用诱导的Gag特异性细胞免疫反应抑制作用并不明显.

Anti-adenovirus neutralizing antibodies and Gag-specific cellular immune responses in Macaca fascicularis immunized with Ad5-HIVgag

Objective To observe the level of anti-adenovirus neutralizing antibodies and Gagspecific cellular immune responses in Macaca fascicularis immunized with different dosage of recombinant adenovirus vaccine Ad5-HIVgag by repeated intramuscular injection.Methods The Macaca fascicularis were randomly divided into four groups of 6.Different amount of the purified Ad5-HIVgag(0.99 × 1011 VP,4.94 × 1011 VP,24.68 × 1011 VP) or PBS were administered in 3 weeks interval and five times.The level of anti-adenovims neutralizing antibodies and Gag-specific cellular immune responses at different time points were detected by neutralization assay and Elispot assay respectively.Results High level of anti-adenovirus neutralizing antibodies could be detected in three groups immunized with Ad5-HIVgag at 3 weeks after first immunization.The neutralizing antibodies reached peak at 8 weeks after primary immunization,and declined slightly at late time.Significant HIV-1 Gag-specific cellular immune responses were detected in all Ad5-HIVgag immunized groups at 5 weeks post first immunization.The Gag-specific cellular immune responses declined at 12 weeks and then increased with time.Conclusion Anti-adenovirus neutralizing antibodies could be induced in Macaca fascicularis immunized with Ad5-HIVgag by repeated intramuscular injection.And the Gag-specific cellular immune responses tended to increase with the injection times.The presence of anti-adenovirus neutralizing antibodies induced by vaccination with adenovirus vectors in Ad5-naive animals did not further reduce Gag-specific cellular immune responses.