Chen Z, Matsuo K, Asanuma H, Takahashi H, Iwasaki T, Suzuki Y, Aizawa C, Kurata T, Tamura S
Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
Vaccine. 1999 Feb 26;17(7-8):653-9. doi: 10.1016/s0264-410x(98)00247-3.
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 microg 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 titers 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 M -expressing plasmid DNA to this mixture does not enhance the degree of protection afforded.
在BALB/c小鼠中检测了编码甲型流感病毒A/PR/8/34（PR8）（H1N1）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混合物（HA + NA和HA + NA + M1）预防同源或异源病毒感染的能力。通过粒子介导的DNA转移至表皮（基因枪），以每只小鼠1微克各组分的剂量，对每种DNA进行两次接种，间隔3周，或四次接种，间隔2周。末次免疫7天后，用致死剂量的同源或异源病毒攻击小鼠，并通过观察肺病毒滴度和存活率来评估每种DNA保护小鼠免受流感侵害的能力。给予（HA + NA）或（HA + NA + M1）质粒DNA混合物可提供几乎完全的保护，抵御PR8病毒攻击，且这种保护伴随着对各组分的高水平特异性抗体反应。这些组提供的保护程度显著高于单独给予表达HA或NA的DNA的小鼠，单独给予表达HA或NA的DNA只能提供部分保护抵御PR8攻击，也高于给予表达M1的DNA的小鼠，给予表达M1的DNA未能提供任何保护。此外，两种质粒DNA混合物（HA + NA）和（HA + NA + M1）均显示出对A/山形/120/86（H1N1）病毒攻击提供交叉保护的轻微趋势，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混合物在提供针对PR8或异源病毒攻击的保护能力方面没有明显差异。这些结果表明，在通过基因枪免疫的小鼠中，编码HA和NA的质粒DNA混合物可提供最有效的保护，抵御病毒攻击。向该混合物中添加表达M的质粒DNA不会增强所提供的保护程度。
