Single-Dose Vaccination of a Recombinant Parainfluenza Virus 5 Expressing NP from H5N1 Virus Provides Broad Immunity against Influenza A Viruses
Single-Dose Vaccination of a Recombinant Parainfluenza Virus 5 Expressing NP from H5N1 Virus Provides Broad Immunity against Influenza A Viruses
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DOI：
10.1128/jvi.00120-13
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发表时间：
2013-05-01
影响因子：
5.4
通讯作者：
He, Biao
中科院分区：
文献类型：
--
作者：
Li, Zhuo;Gabbard, Jon D.;He, Biao
流感病毒通常通过抗原漂移和转移逃避宿主免疫，尽管以前曾感染过流感病毒和/或接种过疫苗。需要与流行病毒株相匹配的疫苗才能获得最佳保护。开发一种提供广泛交叉保护免疫的通用流感病毒疫苗将是非常重要的。甲型流感病毒的核蛋白(NP)在所有甲型流感病毒株中高度保守，已被探索作为一种通用的流感病毒疫苗的抗原。在本工作中，我们从高致病性禽流感病毒H5N1(A/越南/1203/2004)和L(PIV5-NP-HN/L)之间构建了含有NP的重组副流感病毒5(PIV5)，并对其效果进行了检测。PIV5-NP-HN/L诱导小鼠体液和T细胞应答。一次接种pIV5-NP-HN/L对致死性H1N1病毒攻击有完全保护作用，对致死性H5N1 HPAI病毒攻击有50%保护作用。为了提高疗效，NP被插入到PIV5基因组的不同位置。在F和SH之间或SH和HN之间含有NP的重组PIV5(PIV5-NP-F/SH)比PIV5-NP-HN/L具有更好的抗H5N1 HPAI病毒攻击的能力。这些结果表明，表达H5N1 NP的PIV5有可能被用作通用流感病毒疫苗。
Influenza viruses often evade host immunity via antigenic drift and shift despite previous influenza virus infection and/or vaccination. Vaccines that match circulating virus strains are needed for optimal protection. Development of a universal influenza virus vaccine providing broadly cross-protective immunity will be of great importance. The nucleoprotein (NP) of influenza A virus is highly conserved among all strains of influenza A viruses and has been explored as an antigen for developing a universal influenza virus vaccine. In this work, we generated a recombinant parainfluenza virus 5 (PIV5) containing NP from H5N1 (A/Vietnam/1203/2004), a highly pathogenic avian influenza (HPAI) virus, between HN and L (PIV5-NP-HN/L) and tested its efficacy. PIV5-NP-HN/L induced humoral and T cell responses in mice. A single inoculation of PIV5-NP-HN/L provided complete protection against lethal heterosubtypic H1N1 challenge and 50% protection against lethal H5N1 HPAI virus challenge. To improve efficacy, NP was inserted into different locations within the PIV5 genome. Recombinant PIV5 containing NP between F and SH (PIV5-NP-F/SH) or between SH and HN (PIV5-NP-SH/HN) provided better protection against H5N1 HPAI virus challenge than did PIV5-NP-HN/L. These results suggest that PIV5 expressing NP from H5N1 has the potential to be utilized as a universal influenza virus vaccine.