Enhanced protection against a lethal influenza virus challenge by immunization with both hemagglutinin- and neuraminidase-expressing DNAs
Enhanced protection against a lethal influenza virus challenge by immunization with both hemagglutinin- and neuraminidase-expressing DNAs
复制标题
DOI：
10.1016/s0264-410x(98)00247-3
复制
发表时间：
1999-02-26
期刊：
影响因子：
5.5
通讯作者：
Tamura, S
中科院分区：
文献类型：
--
作者：
Chen, Z;Matsuo, K;Tamura, S
在BALB/c小鼠中检测了编码流感病毒A/PR/8/34 （H1N1）的血凝素（HA）、神经氨酸酶（NA）或基质蛋白（M1）的质粒DNA，以及这些质粒DNA （HA + NA和HA + NA + M1）的混合物对同源或异源病毒感染的保护能力。每个DNA分别接种2次，间隔3周，或4次，间隔2周，剂量为每只小鼠1 μ g，通过颗粒介导的DNA转移到表皮（基因枪）。最后一次免疫后7天，用致死性同源或异源病毒攻击小鼠，通过观察肺病毒升数和存活率来评估每种DNA保护小鼠免受流感的能力。质粒DNA混合物（HA + NA）或（HA + NA + M1）对PR8病毒的攻击提供了几乎完全的保护，并且这种保护伴随着对各自成分的高水平特异性抗体反应。这些组提供的保护程度明显高于单独给予表达HA或na的DNA的小鼠，它们对PR8的攻击只提供部分保护，也高于给予表达m1的DNA的小鼠，后者没有提供任何保护。此外，质粒DNA混合物（HA + NA）和（HA + NA + M1）都显示出对a/ Yamagata/120/86 （H1N1）病毒攻击提供交叉保护的轻微倾向，并且伴随着相对高水平的交叉反应抗体。因此，HA + NA和HA + NA + M1质粒DNA混合物在抵抗PR8或异源病毒攻击方面的保护能力没有明显差异。这些结果表明，在基因枪免疫小鼠中，编码HA和NA的质粒dna的混合物可以提供最有效的病毒攻击保护。向混合物中加入表达m1的质粒DNA并不能提高所提供的保护程度。1999爱思唯尔科学有限公司版权所有。
The ability of plasmid DNA encoding hemagglutinin (HA), neuraminidase (NA) or matrix protein (M1) from influenza virus A/PR/8/34 (PR8) (H1N1), and mixtures of these plasmid DNAs (HA + NA and HA + NA + M1) to protect against homologous or heterologous virus infection was examined in BALB/c mice. Each DNA was inoculated twice, 3 weeks apart, or four times, 2 weeks apart, at a dose of 1 mu g of each component per mouse by particle-mediated DNA transfer to the epidermis (gene gun). Seven days after the last immunization, mice were challenged with a lethal homologous or heterologous virus and the ability of each DNA to protect the mice from influenza was evaluated by observing lung virus liters and survival rates. The administration of a plasmid DNA mixture of either (HA + NA) or (HA + NA + M1) provided almost complete protection against the PR8 virus challenge, and this protection was accompanied by high levels of specific antibody responses to the respective components. The degree of protection afforded in these groups is significantly higher than that in mice given either HA- or NA-expressing DNA alone, which provided only a partial protection against PR8 challenge or that in mice given M1-expressing DNA, which failed to provide any protection. In addition: both of the plasmid DNA mixtures (HA + NA) and (HA + NA + M1) showed a slight tendency to provide cross-protection against an A/Yamagata/120/86 (H1N1) virus challenge, and this was accompanied by a relatively high level of cross-reacting antibodies. Thus, there was no clear difference between the ability of the HA + NA and HA + NA + M1 plasmid DNA mixtures in providing protection against either a PR8 or heterologous virus challenge. These results suggest that in mice immunized by gene gun, a mixture of plasmid DNAs encoding HA and NA can provide the most effective protection against the virus challenge. The addition of the M1-expressing plasmid DNA to this mixture does not enhance the degree of protection afforded. (C) 1999 Elsevier Science Ltd. All rights reserved.