Adverse effects of feline IL-12 during DNA vaccination against feline infectious peritonitis virus
Adverse effects of feline IL-12 during DNA vaccination against feline infectious peritonitis virus
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DOI：
10.1099/0022-1317-83-1-1
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发表时间：
2002-01-01
影响因子：
3.8
通讯作者：
Rottier，PJM
中科院分区：
文献类型：
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作者：
Glansbeek，HL;Haagmans，BL;Rottier，PJM
细胞介导的免疫被认为在保护猫免受猫传染性腹膜炎（FIP）（一种进行性和致命的冠状病毒疾病）方面起着决定性作用。鉴于DNA疫苗诱导细胞介导的应答的潜力，评价了其在猫中诱导保护性免疫的效力。选择膜（M）和核衣壳（N）蛋白作为抗原，因为已知针对FIP病毒（FIPV）刺突（S）蛋白的抗体可促进发病。然而，通过重复注射编码这些蛋白质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，初免-加强方案未能提供保护，其中使用质粒DNA进行初免并使用表达相同冠状病毒蛋白的重组牛痘病毒进行加强。由于IL-12在启动细胞介导的免疫中的作用，研究了编码猫细胞因子的质粒的共递送的作用。同样，IL-12没有达到预期-相反，它增强了对FIPV攻击的易感性。这项研究表明，DNA疫苗接种未能保护猫免受FIP和IL-12可能会产生不利影响时，用作细胞因子佐剂。
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.