Immunization with recombinant bovine but not mouse prion protein delays the onset of disease in mice inoculated with a mouse-adapted prion

Immunization with recombinant bovine but not mouse prion protein delays the onset of disease in mice inoculated with a mouse-adapted prion
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DOI:
10.1016/j.vaccine.2006.09.078
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发表时间:
2007-01-22
期刊:
影响因子:
5.5
通讯作者:
Sakaguchi, Suehiro
Sakaguchi, Suehiro
中科院分区:
医学3区
文献类型:
--
作者:
Ishibashi, Daisuke;Yamanaka, Hitoki;Sakaguchi, Suehiro

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由于 PrP 是朊病毒的主要成分,宿主对内源性朊病毒蛋白 (PrP) 的耐受性阻碍了朊病毒疫苗的开发。事实上,我们发现用小鼠重组 PrP 免疫小鼠并没有对适应小鼠的朊病毒产生预防作用。然而,有趣的是,在接种小鼠朊病毒后,用重组牛 PrP 免疫的小鼠患上这种疾病的时间明显晚于未免疫的小鼠。绵羊重组 PrP 表现出不同的预防效果。小鼠重组 PrP 仅刺激非常微弱的抗体反应。相比之下,牛重组 PrP 具有更高的免疫原性,并产生不同数量的抗小鼠 PrP 自身抗体。绵羊重组 PrP 也具有免疫原性,但产生的抗 PrP 自身抗体的量变化较大。这些结果可能为朊病毒疫苗的开发开辟新途径。 (c) 2006 Elsevier Ltd. 保留所有权利。
Host tolerance to endogenous prion protein (PrP) has hampered the development of prion vaccines as PrP is a major component of prions. Indeed, we show that immunization of mice with mouse recombinant PrP elicited no prophylactic effect against a mouse-adapted prion. However, interestingly, mice immunized with recombinant bovine PrP developed the disease significantly later than non-immunized mice after inoculation of a mouse prion. Sheep recombinant PrP exhibited variable prophylactic effects. Mouse recombinant PrP stimulated only very weak antibody responses. In contrast, bovine recombinant PrP was higher immunogenic and produced variable amounts of anti-mouse PrP autoantibodies. Sheep recombinant PrP was also immunogenic but produced more variable amounts of anti-PrP autoantibodies. These results might open a new way for development of prion vaccines. (c) 2006 Elsevier Ltd. All rights reserved.