NS-based live attenuated H1N1 pandemic vaccines protect mice and ferrets.

NS-based live attenuated H1N1 pandemic vaccines protect mice and ferrets.
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DOI:
10.1016/j.vaccine.2010.08.106
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发表时间:
2010-11-23
期刊:
影响因子:
5.5
通讯作者:
Wentworth, David E.
Wentworth, David E.
中科院分区:
医学3区
文献类型:
--
作者:
Zhou, Bin;Li, Yan;Belser, Jessica A.;Pearce, Melissa B.;Schmolke, Mirco;Subba, Anju X.;Shi, Zhengli;Zaki, Sherif R.;Blau, Dianna M.;Garcia-Sastre, Adolfo;Tumpey, Terrence M.;Wentworth, David E.

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虽然甲型流感病毒疫苗是对抗感染的最有效方法,但显然需要加快其生产并提高其效力。我们通过合理地将突变直接工程化到大流行性H1N1病毒的基因组中来产生活的减毒人A型流感疫苗(LAIV)。两种LAIV(NS 1 -73和NS 1 -126)是基于LAIV对动物甲型流感病毒的成功。第三个候选者(NSΔ5)是一个独特的NS突变体,从未被用作LAIV。通过分析减毒、干扰素产生、免疫原性及其保护小鼠和雪貂的能力来确定每种LAIV的疫苗潜力。这项研究表明NSΔ5是一种理想的LAIV候选物,提供了关于不同NS突变对大流行性H1N1病毒的影响的重要信息,并表明LAIV可以直接从新出现/流行的甲型流感病毒的基因组中进行工程改造。
Although vaccines against influenza A virus are the most effective method to combat infection, it is clear that their production needs to be accelerated and their efficacy improved. We generated live attenuated human influenza A vaccines (LAIVs) by rationally engineering mutations directly into the genome of a pandemic-H1N1 virus. Two LAIVs (NS1-73 and NS1-126) were based on the success of LAIVs for animal influenza A viruses. A third candidate (NSΔ5) is a unique NS-mutant that has never been used as a LAIV. The vaccine potential of each LAIV was determined through analysis of attenuation, interferon production, immunogenicity, and their ability to protect mice and ferrets. This study demonstrates that NSΔ5 is an ideal LAIV candidate, provides important information on the effects that different NS mutations have on the pandemic-H1N1 virus and shows that LAIVs can be engineered directly from the genomes of emerging/circulating influenza A viruses.
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