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脂质体电荷对用利什曼原虫重组主要表面糖蛋白(rgp63)免疫的BALB/c小鼠产生的免疫反应的作用。

The role of liposome charge on immune response generated in BALB/c mice immunized with recombinant major surface glycoprotein of Leishmania (rgp63).

作者信息

Badiee Ali, Jaafari Mahmoud R, Khamesipour Ali, Samiei Afshin, Soroush Dina, Kheiri Masoumeh Tavassoti, Barkhordari Farzaneh, McMaster W Robert, Mahboudi Fereidoun

机构信息

School of Pharmacy, Biotechnology Research Center and Pharmaceutical Research Center, Mashhad University of Medical Sciences, Vakil-Abad Blvd, P.O. Box 91775-1365, Mashhad, Khorasan, Iran.

出版信息

Exp Parasitol. 2009 Apr;121(4):362-9. doi: 10.1016/j.exppara.2008.12.015. Epub 2009 Jan 1.

Abstract

Liposomes as a lipid-based system have been shown to be an effective adjuvant formulation. In this study, the role of liposome charge in induction of a Th1 type of immune response and protection against leishmaniasis in BALB/c mice was studied. Liposomes containing rgp63 were prepared by Dehydration-Rehydration Vesicle (DRV) method. Neutral liposomes consisted of dipalmitoylphosphatidylcholine and cholesterol. Positively and negatively charged liposomes were prepared by adding dimethyldioctadecylammonium bromide (DDAB) or dicetyl phosphate (DCP) to the neutral liposome formulation, respectively. Female BALB/c mice were immunized subcutaneously with negatively, positively charged or neutral liposomes encapsulated with rgp63, rgp63 in soluble form or PBS, three times in 3week intervals. The extent of protection and type of immune response generated were studied in different groups of mice. The group of mice immunized with rgp63 encapsulated in neutral liposomes showed a significantly (P<0.01) smaller footpad swelling upon challenge with Leishmania major compared with positively or negatively charged liposomes. The mice immunized with neutral liposomes also showed a significantly (P<0.01) the lowest splenic parasite burden, the highest IgG2a/IgG1 ratio and IFN-gamma production and the lowest IL-4 level compared to the other groups. The results indicated that a Th1 type of immune response was induced in mice immunized with neutral liposomes more efficiently than positively charged liposomes and conversely negatively charged liposomes induced a Th2 type of immune response.

摘要

脂质体作为一种基于脂质的系统,已被证明是一种有效的佐剂制剂。在本研究中,研究了脂质体电荷在诱导BALB/c小鼠Th1型免疫反应和预防利什曼病中的作用。通过脱水-再水化囊泡(DRV)法制备了含有rgp63的脂质体。中性脂质体由二棕榈酰磷脂酰胆碱和胆固醇组成。分别通过向中性脂质体制剂中添加二甲基二十八烷基溴化铵(DDAB)或十六烷基磷酸酯(DCP)来制备带正电荷和负电荷的脂质体。雌性BALB/c小鼠皮下注射包裹有rgp63的带负电荷、正电荷或中性脂质体、可溶性形式的rgp63或PBS,每隔3周免疫3次。在不同组的小鼠中研究了产生的保护程度和免疫反应类型。与带正电荷或负电荷的脂质体相比,用包裹在中性脂质体中的rgp63免疫的小鼠组在用硕大利什曼原虫攻击后足垫肿胀明显更小(P<0.01)。与其他组相比,用中性脂质体免疫的小鼠还表现出脾脏寄生虫负荷显著最低(P<0.01)、IgG2a/IgG1比率最高、IFN-γ产生最高以及IL-4水平最低。结果表明,与带正电荷的脂质体相比,用中性脂质体免疫的小鼠更有效地诱导了Th1型免疫反应,相反,带负电荷的脂质体诱导了Th2型免疫反应。

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