Live, attenuated coronavirus vaccines through the directed deletion of group-specific genes provide protection against feline infectious peritonitis
Live, attenuated coronavirus vaccines through the directed deletion of group-specific genes provide protection against feline infectious peritonitis
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DOI：
10.1128/jvi.78.8.3863-3871.2004
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发表时间：
2004-04-01
影响因子：
5.4
通讯作者：
Rottier, PJM
中科院分区：
文献类型：
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作者：
Haijema, BJ;Volders, H;Rottier, PJM
猫传染性腹膜炎（FIP）是一种致命的免疫介导疾病，由普遍存在的冠状病毒突变体引起。由于之前在实验室和现场条件下保护猫的尝试基本上不成功，因此我们使用我们最近开发的反向遗传学系统（B. J. Haijema、H. Volders 和 P. J. M. Rottier, J. Virol. 77:4528-4538, 2003）来开发改良的 FIP 活疫苗。为此，我们删除了群体特异性基因簇开放阅读框3abc或7ab，获得了删除突变病毒，该病毒不仅在细胞培养物中繁殖良好，而且在猫中表现出减毒表型。在野生型病毒致命的剂量下，基因缺失的突变体不会引起任何临床症状。然而，从高水平的病毒中和抗体来看，它们仍然诱导了免疫反应。缺少 3abc 簇的 FIP 病毒 (FIPV) 突变体以及在较小程度上缺少 7ab 簇的突变体可以保护猫免受致命的同源攻击；缺乏这两个基因簇的突变体没有获得保护。我们的研究表明，从冠状病毒基因组中删除特定群体的基因可产生针对 FIPV 的减毒活候选疫苗。更一般地说，我们的方法可能有助于开发针对其他致病性冠状病毒感染的疫苗，包括引起人类严重急性呼吸道综合症的冠状病毒。
Feline infectious peritonitis (FIP) is a fatal immunity-mediated disease caused by mutants of a ubiquitous coronavirus. Since previous attempts to protect cats under laboratory and field conditions have been largely unsuccessful, we used our recently developed system of reverse genetics (B. J. Haijema, H. Volders, and P. J. M. Rottier, J. Virol. 77:4528-4538, 2003) for the development of a modified live FIP vaccine. With this objective, we deleted the group-specific gene cluster open reading frame 3abc or 7ab and obtained deletion mutant viruses that not only multiplied well in cell culture but also showed an attenuated phenotype in the cat. At doses at which the wild-type virus would be fatal, the mutants with gene deletions did not cause any clinical symptoms. They still induced an immune response, however, as judged from the high levels of virus-neutralizing antibodies. The FIP virus (FIPV) mutant lacking the 3abc cluster and, to a lesser extent, the mutant missing the 7ab cluster, protected cats against a lethal homologous challenge; no protection was obtained with the mutant devoid of both gene clusters. Our studies show that the deletion of group-specific genes from the coronavirus genome results in live attenuated candidate vaccines against FIPV. More generally, our approach may allow the development of vaccines against infections with other pathogenic coronaviruses, including that causing severe acute respiratory syndrome in humans.