Toxoplasma gondii cathepsin proteases are undeveloped prominent vaccine antigens against toxoplasmosis.
Toxoplasma gondii cathepsin proteases are undeveloped prominent vaccine antigens against toxoplasmosis.
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弓形虫组织蛋白酶是尚未开发的针对弓形虫病的重要疫苗抗原
DOI：
10.1186/1471-2334-13-207
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发表时间：
2013-05-07
影响因子：
3.7
通讯作者：
He S
中科院分区：
文献类型：
--
作者：
Zhao G;Zhou A;Lv G;Meng M;Sun M;Bai Y;Han Y;Wang L;Zhou H;Cong H;Zhao Q;Zhu XQ;He S
背景
刚地弓形虫是一种专性细胞内顶复体寄生虫，可感染包括人类在内的多种温血动物。t.弓形虫表达半胱氨酸蛋白酶C1家族的五个成员，包括组织蛋白酶B样（TgCPB）和组织蛋白酶L样（TgCPL）蛋白。TgCPB参与ROP蛋白成熟和寄生虫入侵，而TgCPL有助于proTgM2AP和proTgMIC3的蛋白水解成熟。TgCPL也与细胞分裂后寄生虫空泡中的残留体有关。这两种蛋白酶都是T.刚地。本研究的目的是探讨TgCPB和TgCPL作为T.刚地。
方法
利用生物信息学方法，我们分析了TgCPB和TgCPL蛋白，并确定了几个线性B细胞表位和潜在的Th细胞表位。在此基础上，我们构建了两个单基因构建体（TgCPB和TgCPL）和一个多基因构建体（pTgCPB/TgCPL），并将其免疫BALB/c小鼠，测试它们作为DNA疫苗的有效性。
结果
TgCPB和TgCPL疫苗在小鼠中引起强烈的体液和细胞免疫应答，这两者都是Th-1细胞介导的。此外，所有的疫苗都能保护小鼠免受强毒T。弓形虫RH速殖子，多基因疫苗（pTgCPB/TgCPL）提供最高水平的保护。
结论
t.弓形虫CPB和CPL蛋白酶是开发为新型DNA疫苗的强有力的候选者。
Background
Toxoplasma gondii, an obligate intracellular apicomplexan parasite, infects a wide range of warm-blooded animals including humans. T. gondii expresses five members of the C1 family of cysteine proteases, including cathepsin B-like (TgCPB) and cathepsin L-like (TgCPL) proteins. TgCPB is involved in ROP protein maturation and parasite invasion, whereas TgCPL contributes to proteolytic maturation of proTgM2AP and proTgMIC3. TgCPL is also associated with the residual body in the parasitophorous vacuole after cell division has occurred. Both of these proteases are potential therapeutic targets in T. gondii. The aim of this study was to investigate TgCPB and TgCPL for their potential as DNA vaccines against T. gondii.
Methods
Using bioinformatics approaches, we analyzed TgCPB and TgCPL proteins and identified several linear-B cell epitopes and potential Th-cell epitopes in them. Based on these results, we assembled two single-gene constructs (TgCPB and TgCPL) and a multi-gene construct (pTgCPB/TgCPL) with which to immunize BALB/c mice and test their effectiveness as DNA vaccines.
Results
TgCPB and TgCPL vaccines elicited strong humoral and cellular immune responses in mice, both of which were Th-1 cell mediated. In addition, all of the vaccines protected the mice against infection with virulent T. gondii RH tachyzoites, with the multi-gene vaccine (pTgCPB/TgCPL) providing the highest level of protection.
Conclusions
T. gondii CPB and CPL proteases are strong candidates for development as novel DNA vaccines.
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DOI：
10.1084/jem.182.5.1591
发表时间：
1995-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Constant S;Pfeiffer C;Woodard A;Pasqualini T;Bottomly K
通讯作者：
Bottomly K
影响因子：
1.5
作者：
Huang, Robert;Que, Xuchu;Hirata, Ken;Brinen, Linda S.;Lee, Ji Hyun;Hansell, Elizabeth;Engel, Juan;Sajid, Mohammed;Reed, Sharon
通讯作者：
Reed, Sharon
弓形虫免疫图谱蛋白-1 (TgIMP1) 是一种针对弓形虫病的新型候选疫苗
影响因子：
5.5
作者：
Cui, Xia;Lei, Tao;Liu, Qun
通讯作者：
Liu, Qun
影响因子：
3.7
作者：
Haroon F;Händel U;Angenstein F;Goldschmidt J;Kreutzmann P;Lison H;Fischer KD;Scheich H;Wetzel W;Schlüter D;Budinger E
通讯作者：
Budinger E
影响因子：
--
作者：
Dou, Zhicheng;Carruthers, Vern B.
通讯作者：
Carruthers, Vern B.