Nitschke Cindy, Flechsig Eckhard, van den Brandt Jens, Lindner Nele, Lührs Thorsten, Dittmer Ulf, Klein Michael A
Institute of Virology and Immunobiology, University of Wuerzburg, Versbacherstr. 7, D-97078 Wuerzburg, Germany.
Vet Microbiol. 2007 Aug 31;123(4):367-76. doi: 10.1016/j.vetmic.2007.03.032. Epub 2007 Apr 5.
Vaccination against prion diseases constitutes a promising approach for the treatment and prevention of the disease. Passive immunisation with antibodies binding to the cellular prion protein (PrP(C)) can protect against prion disease. However, immunotherapeutic strategies with active immunisation are limited due to the immune tolerance against the self-antigen. In order to develop an anti-prion vaccine, we designed a novel DNA fusion vaccine composed of mouse PrP and immune stimulatory helper T-cell epitopes of the tetanus toxin that have previously been reported to break tolerance to other self-antigens. This approach provoked a strong PrP(C)-specific humoral and cellular immune response in PrP null mice, but only low antibody titres were found in vaccinated wild-type mice. Furthermore, prime-boost immunisation with the DNA vaccine and recombinant PrP protein increased antibody titres in PrP null mice, but failed to protect wild-type mice from mouse scrapie.
针对朊病毒疾病的疫苗接种是治疗和预防该疾病的一种有前景的方法。用与细胞朊蛋白（PrP(C)）结合的抗体进行被动免疫可以预防朊病毒疾病。然而，由于对自身抗原的免疫耐受，主动免疫的免疫治疗策略受到限制。为了开发一种抗朊病毒疫苗，我们设计了一种新型DNA融合疫苗，该疫苗由小鼠PrP和破伤风毒素的免疫刺激辅助性T细胞表位组成，此前有报道称这些表位可打破对其他自身抗原的耐受。这种方法在PrP基因敲除小鼠中引发了强烈的PrP(C)特异性体液免疫和细胞免疫反应，但在接种疫苗的野生型小鼠中仅发现低抗体滴度。此外，用DNA疫苗和重组PrP蛋白进行初免-加强免疫可提高PrP基因敲除小鼠的抗体滴度，但未能保护野生型小鼠免受小鼠瘙痒病的侵害。
