Influenza B Virus NS1-Truncated Mutants: Live-Attenuated Vaccine Approach
Influenza B Virus NS1-Truncated Mutants: Live-Attenuated Vaccine Approach
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DOI：
10.1128/jvi.01213-08
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发表时间：
2008-11-01
影响因子：
5.4
通讯作者：
Palese, Peter
中科院分区：
文献类型：
--
作者：
Hai, Rong;Martinez-Sobrido, Luis;Palese, Peter
B型流感病毒可在人群中引起大量发病率和死亡率，疫苗接种仍然是迄今为止预防这些病毒感染的最佳手段。在这里，我们报告的突变型流感B病毒的建设，作为改进的活病毒疫苗候选人的潜在用途。采用反向遗传学，我们改变了NS 1基因，该基因编码I型干扰素（IFN）拮抗剂。由此产生的NS 1突变体病毒诱导IFN，因此，被发现在体外和体内被减弱。证实NS 1突变体在BALB/c和C57 BL/6 PKR-/-小鼠中均不具有致病性。我们还提供了证据表明，流感B病毒NS 1突变体诱导自我佐剂免疫反应，并赋予有效的保护，以防止攻击与同源和异源B病毒株在小鼠中。
Type B influenza viruses can cause substantial morbidity and mortality in the population, and vaccination remains by far the best means of protection against infections with these viruses. Here, we report the construction of mutant influenza B viruses for potential use as improved live-virus vaccine candidates. Employing reverse genetics, we altered the NS1 gene, which encodes a type I interferon (IFN) antagonist. The resulting NS1 mutant viruses induced IFN and, as a consequence, were found to be attenuated in vitro and in vivo. The absence of pathogenicity of the NS1 mutants in both BALB/c and C57BL/6 PKR-/- mice was confirmed. We also provide evidence that influenza B virus NS1 mutants induce a self-adjuvanted immune response and confer effective protection against challenge with both homologous and heterologous B virus strains in mice.