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弓形虫蛋白酶抑制剂-1(TgPI-1)是一种新型的抗弓形虫病疫苗候选物。

Toxoplasma gondii protease inhibitor-1 (TgPI-1) is a novel vaccine candidate against toxoplasmosis.

作者信息

Cuppari Anahi Fernandez, Sanchez Vanesa, Ledesma Bibiana, Frank Fernanda M, Goldman Alejandra, Angel Sergio O, Martin Valentina

机构信息

Laboratorio de Inmunología, Centro de Salud y Medio Ambiente, E.C.y T., Universidad de Gral. San Martín, Provincia de Buenos Aires, Argentina.

出版信息

Vaccine. 2008 Sep 15;26(39):5040-5. doi: 10.1016/j.vaccine.2008.07.031. Epub 2008 Aug 21.

DOI:10.1016/j.vaccine.2008.07.031
PMID:18675873
Abstract

The Toxoplasma gondii serin protease inhibitor-1 (TgPI-1) is a dense granule antigen that showed to specifically inhibit trypsin, chymotrypsin and neutrophil elastase, suggesting a possible modulatory role during the parasite invasion process and on the development of the innate immune response. To study the immune-protective value of TgPI-1, C3H/HeN mice were immunized with a recombinant form of the antigen rTgPI-1 combined with alum. All immunized mice produced specific anti-rTgPI-1 immunoglobulins, with high IgG antibody titers and a mixed IgG(1)/IgG(2a) response, with predominance of IgG(1) production. The cellular immune response was associated with the production of IFN-gamma and IL-10 cytokines. Vaccinated mice displayed significant protection against an oral challenge either after a lethal infection with Me49 cysts (90% survival vs. 50%) and also after a non-lethal infection (58% reduction in brain parasite load) compared to the non-vaccinated control group. In conclusion, rTgPI-1 elicits a strong specific immune response providing partial protection against both T. gondii acute and chronic infection, so it would be a good candidate in a vaccine against toxoplasmosis, which could be combined with other relevant parasite antigens.

摘要

弓形虫丝氨酸蛋白酶抑制剂-1(TgPI-1)是一种致密颗粒抗原,已证明其能特异性抑制胰蛋白酶、糜蛋白酶和中性粒细胞弹性蛋白酶,这表明它在寄生虫入侵过程以及先天免疫反应的发展中可能发挥调节作用。为了研究TgPI-1的免疫保护价值,用重组抗原rTgPI-1与明矾联合免疫C3H/HeN小鼠。所有免疫小鼠均产生了特异性抗rTgPI-1免疫球蛋白,IgG抗体滴度高,呈现IgG(1)/IgG(2a)混合应答,且以IgG(1)产生为主。细胞免疫反应与IFN-γ和IL-10细胞因子的产生有关。与未接种疫苗的对照组相比,接种疫苗的小鼠在经Me49囊肿致死性感染后(存活率90% vs. 50%)以及非致死性感染后(脑内寄生虫负荷降低58%),对口服攻击均表现出显著的保护作用。总之,rTgPI-1能引发强烈的特异性免疫反应,对弓形虫急性和慢性感染均提供部分保护,因此它可能是抗弓形虫病疫苗的良好候选物,可与其他相关寄生虫抗原联合使用。

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