Khoshgoo Naghmeh, Zahedifard Farnaz, Azizi Hiva, Taslimi Yasaman, Alonso Maribel Jiménez, Rafati Sima
Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
Vaccine. 2008 Oct 29;26(46):5822-9. doi: 10.1016/j.vaccine.2008.08.065. Epub 2008 Sep 18.
Visceral leishmaniasis is the most acute form of leishmaniasis and vaccination is the best approach to control it. One of the major groups of virulence factors in Leishmania belongs to cysteine proteinase family. In this study, for the first time, the protective potential of Leishmania infantum cysteine proteinase type III (CPC) by using a prime-boost strategy is evaluated in BALB/c mice. The experiment was carried out in three groups of mice. Vaccinated group was primed with pcDNA-cpc and boosted with rCPC-DHFR in combination with CpG motif and Montanide 720 as adjuvant. Control groups received pcDNA and rDHFR or PBS. The ratio of IgG2a/IgG1, nitric oxide concentration and IFN-gamma induction in vaccinated group is significantly higher than controls. Furthermore, the parasite load of vaccinated group is significantly lower than controls. In addition, sera reactivity of visceral leishmaniasis individuals was examined and showed considerable reactivities toward rCPC in comparison with cutaneous leishmaniasis. The achieved result is highly encouraging the use of cysteine proteinases types I, II and III as vaccine candidate against visceral leishmaniasis.
内脏利什曼病是利什曼病最急性的形式，疫苗接种是控制该病的最佳方法。利什曼原虫的主要毒力因子组之一属于半胱氨酸蛋白酶家族。在本研究中，首次在BALB/c小鼠中评估了利用初免-加强策略的婴儿利什曼原虫III型半胱氨酸蛋白酶（CPC）的保护潜力。实验在三组小鼠中进行。接种组用pcDNA-cpc进行初免，并用rCPC-DHFR与CpG基序和Montanide 720作为佐剂联合进行加强免疫。对照组接受pcDNA和rDHFR或PBS。接种组中IgG2a/IgG1的比例、一氧化氮浓度和IFN-γ诱导水平显著高于对照组。此外，接种组的寄生虫负荷显著低于对照组。另外，对内脏利什曼病患者的血清反应性进行了检测，结果显示与皮肤利什曼病相比，其对rCPC有相当高的反应性。所取得的结果非常鼓舞人心，有望将I型、II型和III型半胱氨酸蛋白酶用作抗内脏利什曼病的候选疫苗。
