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

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0，14，28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∶512（鼻腔免疫）和1∶10000（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25×10⁸个食蟹疟子孢子攻击，对照组5只恒河猴在攻击后10～14d全部感染，其中1只在攻击后21d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20d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19d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，对食蟹疟攻击具有良好的交叉免疫保护作用。

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

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 x 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 19th 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.