重组霍乱毒素B亚基与恶性疟原虫多抗原表位融合蛋白对恒河猴的免疫保护作用研究  

Induction of Protective Immunity in Rhesus Monkey by Inoculation with Recombinant Fusion Protein of Cholera Toxin B Subunit-Multivalent Epitopes of Plasmodium falciparum

作　　者：李平[1] 钟辉[1] 石成华[1] 李杰之[1] 张艳红[1] 李楚芳[1] 时运林[2] 马清钧[1] 曹诚[1] 

机构地区：[1]军事医学科学院生物工程研究所，北京100850 [2]军事医学科学院微生物与流行病研究所，北京100071

出　　处：《生物工程学报》2004年第4期516-519,共4页Chinese Journal of Biotechnology

基　　金：国家高技术发展计划 ( 863 )项目资助 (No .2 0 0 1AA2 15 0 2 1)~~

摘　　要：使用重组霍乱毒素B亚基 (CTB)与恶性疟原虫抗原表位融合蛋白 (AWTE)免疫恒河猴 ,研究其免疫应答并观察对食蟹疟原虫攻击的保护作用。结果表明 :在 0 ,1 4 ,2 8天分别通过鼻腔和肌肉注射免疫恒河猴 ,第 3次免疫后2周 ,抗CTB抗体平均滴度可达 1∶5 1 2 (鼻腔免疫 )和 1∶1 0 0 0 0 (肌肉免疫 ) ;肌肉免疫后抗疟原虫抗体滴度也显著高于鼻腔免疫组。用 1 2 5× 1 0 8个食蟹疟子孢子攻击 ,对照组 5只恒河猴在攻击后 1 0～ 1 4d全部感染 ,其中 1只在攻击后 2 1d死亡 ,另 4只重度感染 ,感染持续 30d以上。鼻腔免疫组的 5只动物均在攻击 2 0d后出现原虫 ,其中 3只轻度感染 ,感染持续 4d后即恢复 ,其余 2只感染持续 36d以上。肌肉注射组 3只未受感染 ,其余 2只在攻击后 1 9d后轻度感染 ,感染 4d后即完全恢复。以上结果表明 ,使用霍乱毒素B亚基为载体蛋白构建的重组疟疾疫苗具有良好的免疫原性 。Rhesus monkeys (5 in each group) were inoculated with recombinant fusion protein of cholera toxin B subunit and multi valent epitopes of Plasmodium falciparum intranasal or intramuscular (i.m.). Immune responses and protective effect were evaluated. The antibody titer(Geometry mean) against CTB reached 1∶512 (intranasal) and 1∶10000(i.m) 14 day after 3rd immunization, and antibodies against P.falciparum were also elucidated, the titers in i.m. group were also significantly higher than that in intranasal group. The monkeys were challenged with 1 25×10 8 sporozoites of P.cynomolgi, Patent infection was observed in all 5 monkeys in control group inoculated with PBS in 10～14 days after challenge. Patent infection was also observed in 5 animals inoculated via intranasal and 2 animals in intramuscular group 19 th days after challenge, But the infection last only 4 days in 3 animals in intranasal group and 2 animals in intramuscular group. The results demonstrated that the vaccine candidate could induce protective immune responses in rhesus monkey against the challenge of P.cynomolgi.

关 键 词：疟疾 疫苗 霍乱毒素B亚基 恒河猴 

分 类 号：R392.1[医药卫生—免疫学]