Immunogenicity and protective efficacy of replication-incompetent influenza virus-like particles
Immunogenicity and protective efficacy of replication-incompetent influenza virus-like particles
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DOI：
10.1128/jvi.76.2.767-773.2002
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发表时间：
2002-01-01
影响因子：
5.4
通讯作者：
Kawaoka, Y
中科院分区：
文献类型：
--
作者：
Watanabe, T;Watanabe, S;Kawaoka, Y
尽管流感病毒疫苗在减少严重疾病方面取得了成功，但其功效并不理想。我们在这里描述了完全由cdna产生的复制能力不强的流感病毒样颗粒（VLPs）的免疫原性和保护能力，这些颗粒要么缺乏整个NS1基因（编码NS1和NS2蛋白），要么只有NS2基因。在感染NS基因缺陷VLPs的哺乳动物细胞中，检测到核蛋白，但未检测到其他病毒蛋白，包括血凝素（RA）和神经氨酸酶（NA）。相比之下，被表达NS1但不表达NS2 （NS2敲除）的VLPs感染的细胞表达多种病毒蛋白，包括RA和NA。当使用致死剂量的抗原同源小鼠适应流感病毒时，接种ns2敲除VLPs的小鼠中有94%存活，而接种ns缺陷VLPs的小鼠中只有不到10%存活。这些结果表明，复制能力不足的ns2敲除VLPs有可能作为新型流感疫苗，也可能作为表达完全不相关病原体基因的载体。
Despite the success of influenza virus vaccines in reducing severe illness, their efficacy is suboptimal. We describe here the immunogenicity and protective capacity of replication-incompetent influenza virus-like particles (VLPs) which were generated entirely from cDNAs and lacked either the entire NS gene (encoding both the NS1 and NS2 protein) or only the NS2 gene. In mammalian cells infected with NS gene-deficient VLPs, the nucleoprotein, but not other viral proteins including hemagglutinin (RA) and neuraminidase (NA), was detected. In contrast, cells infected with VLPs expressing NS1 but not NS2 (NS2 knockout) expressed multiple viral proteins, including RA and NA. When challenged with lethal doses of an antigenically homologous mouse-adapted influenza virus, 94% of mice-vaccinated with the NS2-knockout VLPs survived, compared with less than 10% of those given the NS-deficient VLPs. These results demonstrate the potential of replication-incompetent NS2-knockout VLPs as novel influenza vaccines and perhaps also as vectors to express genes from entirely unrelated pathogens.