Transgenic Neospora caninum strains constitutively expressing the bradyzoite NcSAG4 protein proved to be safe and conferred significant levels of protection against vertical transmission when used as live vaccines in mice
Transgenic Neospora caninum strains constitutively expressing the bradyzoite NcSAG4 protein proved to be safe and conferred significant levels of protection against vertical transmission when used as live vaccines in mice
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DOI：
10.1016/j.vaccine.2011.07.091
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发表时间：
2011-10-13
期刊：
影响因子：
5.5
通讯作者：
Alvarez-Garcia, G.
中科院分区：
文献类型：
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作者：
Marugan-Hernandez, V.;Ortega-Mora, L. M.;Alvarez-Garcia, G.
目前，尚无有效的治疗方法或疫苗来预防与牛新孢子虫感染相关的垂直传播或流产。已经对不同的疫苗配方进行了测试，活疫苗在保护方面显示出最有希望的结果。此前，获得了以组成型方式表达缓殖子阶段特异性 NcSAG4 抗原 (Nc-1 SAG4(c)) 的转基因犬新孢子虫，并显示出接种小鼠体内寄生虫的持久性降低。因此，本研究评估了 Nc-1 SAG4(c)1.1 和 Nc-1 SAG4(c)2.1 转基因菌株以及 Nc-1 野生型 (WT) 菌株确定其对小鼠垂直传播和脑新孢子虫病的保护功效，因此，母鼠用每种菌株的 5 x 10(5) 速殖子免疫两次，并在妊娠 7-10 天时用异源和有毒分离株的 2 x 10(6) 速殖子进行攻击，Nc-1 SAG4(c)1.1 菌株提供的保护少于其他转基因菌株 (Nc-1)。事实上，接种 Nc-1 SAG4(c)1.1、Nc-1 SAG4(c)2.1 和 Nc-1 (WT) 菌株的母鼠出生后死亡的比例分别为 40%、7% 和 5.6%。相比之下，未免疫的攻击组的死亡率为 100%。此外，小鼠免受先天性传播；Nc-1 SAG4(c)1.1、Nc-1 SAG4(c)2.1 和 Nc-1 WT 免疫组的垂直传播率分别为 45%、11.1% 和 10.8%，而未接种疫苗的感染组为 94.9%。尽管如此，Nc-1 SAG4(c)2.1 菌株似乎是用作活疫苗的最佳候选者，结果表明其对垂直传播的高水平保护和在小鼠中较低的持久性，使得该转基因菌株比 Nc-1 WT 更安全。保留所有权利。
At present, there is no effective treatment or vaccine to prevent vertical transmission or abortion associated with Neospora caninum infection in cattle. Different vaccine formulations have been assayed, and live vaccines have shown the most promising results in terms of protection. Previously, transgenic N. caninum tachyzoites expressing the bradyzoite stage-specific NcSAG4 antigen in a constitutive manner (Nc-1 SAG4(c) were obtained and showed a reduced persistence of parasite in inoculated mice. Thus, the present study evaluates the Nc-1 SAG4(c)1.1 and Nc-1 SAG4(c)2.1 transgenic strains and the Nc-1 wild-type (WT) strain to determine their protective efficacy against vertical transmission and cerebral neosporosis in mice. Consequently, dams were immunized twice with 5 x 10(5) tachyzoites of each strain and challenged with 2 x 10(6) tachyzoites of a heterologous and virulent isolate at 7-10 days of gestation. The Nc-1 SAG4(c)1.1 strain offered less protection than the other transgenic strain (Nc-1 SAG4(c)2.1) or their ancestor (Nc-1 WT). Indeed, 40%, 7% and 5.6% of the postnatal deaths corresponded to pups from dams vaccinated with Nc-1 SAG4(c)1.1, Nc-1 SAG4(c)2.1 and Nc-1 (WT) strains, respectively. In comparison, the non-immunized challenge group had a 100% mortality rate. In addition, mice were protected against congenital transmission; vertical transmission rates were 45%, 11.1% and 10.8% in the Nc-1 SAG4(c)1.1, Nc-1 SAG4(c)2.1 and Nc-1 WT immunized groups, respectively, vs. 94.9% in the non-vaccinated infected group. However, this protection against the postnatal mortality and the vertical transmission was not associated with a consistent Th1 or Th2-type immune response. Nonetheless, the Nc-1 SAG4(c)2.1 strain appears to be the best candidate for use as a live vaccine, as evidenced by results demonstrating its high levels of protection against vertical transmission and its lower persistence in mice, making this transgenic strain safer than Nc-1 WT. (C) 2011 Elsevier Ltd. All rights reserved.