CAJ | 학술논문

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.
목적 관찰불동제량적중조선병독역묘Ad5-HIVgag반복기내주사면역식해후후,식해후체내산생적선병독중화항체수평급Gag특이성세포면역반응수평,초보탐토선병독중화항체적산생대Gag특이성세포면역반응적영향.방법 장24지식해후수궤분위4조:대조조、저제량조、중제량조、고제량조.매3주면역1차,련속면역5차.면역전급면역후불동시간점용중화실험검측동물체내선병독중화항체수평,용Elispot방법검측Gag특이성세포면역반응수평.결과 초차면역후3주3개실험조동물도검측도료교고수평적선병독중화항체,재초차면역후8주체도고봉,회복기결속시략유하강.초차면역후5주삼개실험조동물도검측도료Gag특이성세포면역반응,제초차면역후12주반응수평유소하강,기타시간점세포반응정축점증고추세,단각제량조간미견명현적량효관계.결론 재일정적제량범위내반복다차응용Ad5-HIVgag면역식해후후,가산생침대선병독적중화항체,수착면역차수적증다Gag특이성세포면역반응유증고추세,Ad5역묘면역후중화항체적산생대Ad5역묘반복응용유도적Gag특이성세포면역반응억제작용병불명현.
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.