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猫白细胞介素-12在针对猫传染性腹膜炎病毒的DNA疫苗接种过程中的不良反应。

Adverse effects of feline IL-12 during DNA vaccination against feline infectious peritonitis virus.

作者信息

Glansbeek Harrie L, Haagmans Bart L, Te Lintelo Eddie G, Egberink Herman F, Duquesne Véronique, Aubert André, Horzinek Marian C, Rottier Peter J M

机构信息

Virology Division, Department of Infectious Diseases and Immunology, Veterinary Faculty, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands1.

Institute of Virology, Erasmus University Rotterdam, Rotterdam, The Netherlands2.

出版信息

J Gen Virol. 2002 Jan;83(Pt 1):1-10. doi: 10.1099/0022-1317-83-1-1.

DOI:10.1099/0022-1317-83-1-1
PMID:11752695
Abstract

Cell-mediated immunity is thought to play a decisive role in protecting cats against feline infectious peritonitis (FIP), a progressive and lethal coronavirus disease. In view of the potential of DNA vaccines to induce cell-mediated responses, their efficacy to induce protective immunity in cats was evaluated. The membrane (M) and nucleocapsid (N) proteins were chosen as antigens, because antibodies to the spike (S) protein of FIP virus (FIPV) are known to precipitate pathogenesis. However, vaccination by repeated injections of plasmids encoding these proteins did not protect kittens against challenge infection with FIPV. Also, a prime-boost protocol failed to afford protection, with priming using plasmid DNA and boosting using recombinant vaccinia viruses expressing the same coronavirus proteins. Because of the role of IL-12 in initiating cell-mediated immunity, the effects of co-delivery of plasmids encoding the feline cytokine were studied. Again, IL-12 did not meet expectations - on the contrary, it enhanced susceptibility to FIPV challenge. This study shows that DNA vaccination failed to protect cats against FIP and that IL-12 may yield adverse effects when used as a cytokine adjuvant.

摘要

细胞介导的免疫被认为在保护猫抵抗猫传染性腹膜炎(FIP)中起决定性作用,FIP是一种进行性致死性冠状病毒疾病。鉴于DNA疫苗诱导细胞介导反应的潜力,评估了其在猫中诱导保护性免疫的功效。选择膜(M)蛋白和核衣壳(N)蛋白作为抗原,因为已知针对FIP病毒(FIPV)刺突(S)蛋白的抗体可引发发病机制。然而,通过重复注射编码这些蛋白的质粒进行疫苗接种并不能保护小猫免受FIPV的攻击感染。此外,一种初免-加强方案也未能提供保护,初免使用质粒DNA,加强使用表达相同冠状病毒蛋白的重组痘苗病毒。由于IL-12在启动细胞介导免疫中的作用,研究了共递送编码猫细胞因子的质粒的效果。同样,IL-12未达预期——相反,它增强了对FIPV攻击的易感性。这项研究表明,DNA疫苗接种不能保护猫抵抗FIP,并且IL-12用作细胞因子佐剂时可能产生不利影响。

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