Development and evaluation of an influenza virus subtype H7N2 vaccine candidate for pandemic preparedness
Development and evaluation of an influenza virus subtype H7N2 vaccine candidate for pandemic preparedness
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DOI：
10.1128/cvi.00174-07
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发表时间：
2007-11-01
影响因子：
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通讯作者：
Donis, Ruben O.
中科院分区：
文献类型：
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作者：
Pappas, Claudia;Matsuoka, Yumiko;Donis, Ruben O.
H7 N2亚型的流感病毒已被引入美国的非商业家禽中，这可能导致2002年和2003年记录的H7 N2病毒向人类传播的事件。如果这种病毒获得人与人之间的传播性，则可被视为对公共卫生的潜在威胁。一种受欢迎的全球大流行准备方法包括为任何潜在的大流行病毒开发大流行前疫苗。为此，我们创建了一种高生长抑制病毒（H7 N2-PR 8），其中包含来自低致病性（H7 N2）病毒株的血凝素和神经氨酸酶基因以及来自人类疫苗株（H1N1）的其余六个基因。使用小鼠模型评价了抗性菌株，以评估其抗原性、安全性和保护效力。使用针对H7 N2-PR 8的雪貂抗体进行的抗原性研究表明，这种病毒与不同年份和谱系的不同H7病毒具有广泛的交叉反应性。用高剂量H7 N2-PR 8接种的小鼠和鸡支持病毒复制但存活，表明该病毒与其他低致病性的禽类病毒相当。为了评估H7 N2-PR 8的保护效力，用两个剂量的福尔马林灭活的H7 N2-PR 8单独或与明矾一起免疫小鼠。随后用来自同源和异源谱系A/Canada/444/04（H7 N3）和A/Netherlands/219/03（H7 N7）的高致病性病毒攻击的接种小鼠显示野生型病毒复制的显著减少。这些研究表明，H7 N2-PR 8在动物模型中具有免疫原性、安全性和保护性;这些是作为大流行前疫苗有资格进行I期人体临床试验的基本属性。
Influenza virus of the H7N2 subtype has been introduced into noncommercial poultry in the United States, and this probably resulted in incidents of transmission of H7N2 virus to humans, documented in 2002 and 2003. This virus could be considered a potential threat to public health if it acquired person-to-person transmissibility. A favored approach for global pandemic preparedness includes development of prepandemic vaccines for any potential pandemic virus. To this end, we created a high-growth reassortant virus (H7N2-PR8) containing the genes for the hemagglutinin and the neuraminidase from a low-pathogenicity (H7N2) virus strain and the remaining six genes from a human vaccine strain (H1N1). The reassortant strain was evaluated to assess its antigenicity, safety, and protective efficacy using a mouse model. Antigenicity studies using ferret antibodies raised against H7N2-PR8 indicated that this virus confers broad cross-reactivity with divergent H7 viruses of different years and lineages. Mice and chickens inoculated with high doses of H7N2-PR8 supported virus replication but survived, indicating that this virus is comparable to other avian viruses of low pathogenicity. To assess the protective efficacy of H7N2-PR8, mice were immunized with two doses of formalin-inactivated H7N2-PR8, alone or with alum. Vaccinated mice subsequently challenged with highly pathogenic viruses from homologous and heterologous lineages A/Canada/444/04 (H7N3) and A/Netherlands/219/03 (H7N7) showed pronounced reduction of wild-type virus replication. These studies indicate that H7N2-PR8 is immunogenic, safe, and protective in animal models; these are the essential attributes to qualify for phase I human clinical trials as a prepandemic vaccine.