恶性疟原虫富组氨酸蛋白2重组蛋白与真核表达质粒免疫特性的比较

目的　探讨以恶性疟原虫富组氨酸蛋白 2 (PfHRP2 )为基础的不同形式的侯选疫苗诱导小鼠免疫应答的特性 ,为包含HRP2的恶性疟红内期疫苗的研制提供实验依据。方法　用重组蛋白TP HRP2及真核表达质粒pcDNA3 1(- ) HRP2免疫BALB c小鼠 ,对抗体应答的动力学及特异性进行分析 ,取脾细胞进行体外增殖实验 ,用免疫血清进行P f.体外生长抑制实验。结果　重组蛋白TP HRP2加福氏佐剂诱导BALB c小鼠产生了高水平的抗体 ,其抗体产生快、持续时间久 ,并具较高的特异性 ,细胞应答被同期激活 ,免疫血清可明显抑制红细胞内发育期疟原虫。重组真核表达质粒pcDNA3 1(- ) HRP2诱导BALB c小鼠产生了较高水平和具有一定特异性的抗体 ,其抗体的产生需要多次免疫和较长时间 ,初始化的脾细胞对抗原再刺激的回忆应答显著 ,但免疫血清对疟原虫的体外生长没有抑制作用。结论　HRP2重组蛋白与真核表达质粒在小鼠具有较为不同的免疫特性 ,HRP2重组蛋白疫苗具有潜在的应用前景

Comparison of Immune Responses Elicited by Recombinant Protein and Eukaryotic Expression Plasmid Based on Histidine Rich Protein 2 of Plasmodium falciparum *

OBJECTIVE: To identify the immune characteristics of different vaccine prototypes based on HRP2 and to provide experimental evidence for developing P. f. blood stage vaccines. METHODS: BALB/c mice were immunized with recombinant protein TP-HRP2 or eukaryotic expression plasmid pcDNA3.1(-)/HRP2. The kinetics and specificities of antibody responses were analyzed. The proliferation tests of spleen cells were done, and P. f. growth inhibition assays were done with immune sera. RESULTS: The mice immunized with TP-HRP2 in Freund's adjuvant produced high-level and high-specificity antibody response. The antibodies appeared rapidly and lasted for a longer time. Cellular responses were induced simultaneously, and the immune sera could inhibit the development of parasite in IRBCs. The mice immunized with pcDNA3.1(-)/HRP2 produced middle-level antibody response which had some specificity, however, the induction of antibodies required repeated inoculation and a longer duration. Immune cells were well primed and the memorial immune response was obvious but the immune sera had no effect on the growth of P.f. in vitro. CONCLUSION: Both the recombinant protein and plasmid DNA based on HRP2 have different immune characteristics in mice. HRP2 recombinant protein has the potential in practical application.