Novel linear DNA vaccines induce protective immune responses against lethal infection with influenza virus type A/H5N1.
Novel linear DNA vaccines induce protective immune responses against lethal infection with influenza virus type A/H5N1.
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DOI：
10.4161/hv.4.6.6177
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发表时间：
2008-11
期刊：
影响因子：
--
通讯作者：
Paessler, Slobodan
中科院分区：
文献类型：
--
作者：
Kendirgi, Frederic;Yun, Nadezda E.;Linde, Nathaniel S.;Zacks, Michele A.;Smith, Jeanon N.;Smith, Jennifer K.;McMicken, Harilyn;Chen, Yin;Paessler, Slobodan
关键词：
针对可能发生的流感大流行的疫苗开发一直具有挑战性。常规疫苗如灭活病毒制剂和减毒活病毒制剂在生产速度和产能方面受到限制。 DNA 疫苗接种已成为对抗流感大流行的传统疫苗的潜在替代方案。在这项研究中，我们使用新型无细胞 DNA 制造工艺 (synDNA™) 来生产针对 A/H5N1 型流感病毒的原型线性 DNA 疫苗。这种synDNA™过程不需要细菌发酵，因此避免了在实际治疗DNA构建体中使用抗生素抗性基因和与抗原基因表达无关的其他核酸序列。在小鼠中评估了表达血凝素和神经氨酸酶蛋白 (H5N1 synDNA™)、单独的血凝素 (H5 synDNA™) 或单独的神经氨酸酶 (N1 synDNA™) 的各种疫苗的功效。其中两种构建体（H5 synDNA™ 和 H5N1 synDNA™）诱导了强大的保护性免疫反应，高达 93% 的治疗小鼠在致命的 A/Vietnam/1203/04 H5N1 流感分离株的致命攻击中幸存下来。结合强大的生物活性和简化的生产足迹，这些特性使得使用我们的 synDNA™ 工艺制备的 DNA 疫苗非常适合作为其他疫苗制剂的替代品。
Vaccine development for possible influenza pandemics has been challenging. Conventional vaccines such as inactivated and live attenuated virus preparations are limited in terms of production speed and capacity. DNA vaccination has emerged as a potential alternative to conventional vaccines against influenza pandemics. In this study, we use a novel, cell-free DNA manufacturing process (synDNA™) to produce prototype linear DNA vaccines against the influenza virus type A/H5N1. This synDNA™ process does not require bacterial fermentation, so it avoids the use of antibiotic resistance genes and other nucleic acid sequences unrelated to the antigen gene expression in the actual therapeutic DNA construct. The efficacy of various vaccines expressing the hemagglutinin and neuraminidase proteins (H5N1 synDNA™), hemagglutinin alone (H5 synDNA™) or neuraminidase alone (N1 synDNA™) was evaluated in mice. Two of the constructs (H5 synDNA™ and H5N1 synDNA™) induced a robust protective immune response with up to 93% of treated mice surviving a lethal challenge of a virulent influenza A/Vietnam/1203/04 H5N1 isolate. In combination with a potent biological activity and simplified production footprint, these characteristics make DNA vaccines prepared with our synDNA™ process highly suitable as alternatives to other vaccine preparations.
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DOI：
10.4161/hv.3.5.4175
发表时间：
2007-09-01
期刊：
HUMAN VACCINES
影响因子：
--
作者：
Jimenez, Gretchen S.;Planchon, Rodrick;Smith, Larry R.
通讯作者：
Smith, Larry R.
影响因子：
5.1
作者：
Chen, ZY;He, CY;Kay, MA
通讯作者：
Kay, MA
影响因子：
5.4
作者：
JOHANSSON, BE;KILBOURNE, ED
通讯作者：
KILBOURNE, ED
影响因子：
5.5
作者：
Chen, Z;Kadowaki, S;Tamura, S
通讯作者：
Tamura, S
影响因子：
12.4
作者：
Chen, ZY;He, CY;Kay, MA
通讯作者：
Kay, MA