Recombinant Parainfluenza Virus 5 Expressing Hemagglutinin of Influenza A Virus H5N1 Protected Mice against Lethal Highly Pathogenic Avian Influenza Virus H5N1 Challenge
Recombinant Parainfluenza Virus 5 Expressing Hemagglutinin of Influenza A Virus H5N1 Protected Mice against Lethal Highly Pathogenic Avian Influenza Virus H5N1 Challenge
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DOI：
10.1128/jvi.02321-12
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发表时间：
2013-01-01
影响因子：
5.4
通讯作者：
He, Biao
中科院分区：
文献类型：
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作者：
Li, Zhuo;Mooney, Alaina J.;He, Biao
安全有效的疫苗是防止高致病性禽流感病毒(HPAI)H5N1在人类人群中大规模爆发的最佳方法。目前FDA批准的H5N1疫苗存在严重局限性。迫切需要一种更有效的H5N1疫苗。副流感病毒5(PIV5)是一种副粘病毒，目前还不知道会导致任何人类疾病。PIV5是一种很有吸引力的疫苗载体。在我们的研究中，表达来自H5N1亚型的H5N1血凝素(HA)基因的活重组PIV5(rPIV5-H5)在小鼠中提供了对致死量HPAI H5N1感染的灭菌免疫。此外，我们还研究了在PIV5基因组的不同位置插入H5N1 HA对基于PIV5的疫苗效力的影响。有趣的是，在先导序列(PIV5的实际启动子)和第一个病毒基因(核蛋白(NP))之间插入H5N1 HA并没有导致病毒存活。H5N1 HA插入NP和下一个基因V/P之间，导致了一种生长有缺陷的病毒。我们发现，在小分子疏水(SH)基因和血凝素神经氨酸酶(HN)基因之间插入H5N1 HA对HPAI H5N1攻击具有最好的免疫力：低至1,000 pfu的剂量就足以保护小鼠免受HPAI H5N1攻击。研究表明，表达H5N1 HA的重组PIV5作为HPAI H5N1疫苗具有很大的潜力。
A safe and effective vaccine is the best way to prevent large-scale highly pathogenic avian influenza virus (HPAI) H5N1 outbreaks in the human population. The current FDA-approved H5N1 vaccine has serious limitations. A more efficacious H5N1 vaccine is urgently needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, is not known to cause any illness in humans. PIV5 is an attractive vaccine vector. In our studies, a single dose of a live recombinant PIV5 expressing a hemagglutinin (HA) gene of H5N1 (rPIV5-H5) from the H5N1 subtype provided sterilizing immunity against lethal doses of HPAI H5N1 infection in mice. Furthermore, we have examined the effect of insertion of H5N1 HA at different locations within the PIV5 genome on the efficacy of a PIV5-based vaccine. Interestingly, insertion of H5N1 HA between the leader sequence, the de facto promoter of PIV5, and the first viral gene, nucleoprotein (NP), did not lead to a viable virus. Insertion of H5N1 HA between NP and the next gene, V/phosphorprotein (V/P), led to a virus that was defective in growth. We have found that insertion of H5N1 HA at the junction between the small hydrophobic (SH) gene and the hemagglutinin-neuraminidase (HN) gene gave the best immunity against HPAI H5N1 challenge: a dose as low as 1,000 PFU was sufficient to protect against lethal HPAI H5N1 challenge in mice. The work suggests that recombinant PIV5 expressing H5N1 HA has great potential as an HPAI H5N1 vaccine.