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猪和人类通用的多价甲型流感DNA疫苗的载体优化及无针皮内接种

Vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine for pigs and humans.

作者信息

Borggren Marie, Nielsen Jens, Bragstad Karoline, Karlsson Ingrid, Krog Jesper S, Williams James A, Fomsgaard Anders

机构信息

a Virus Research and Development Laboratory ; Department of Microbiological Diagnostic and Virology; Statens Serum Institut ; Copenhagen , Denmark.

出版信息

Hum Vaccin Immunother. 2015;11(8):1983-90. doi: 10.1080/21645515.2015.1011987.

Abstract

The threat posed by the 2009 pandemic H1N1 virus emphasized the need for new influenza A virus vaccines inducing a broad cross-protective immune response for use in both humans and pigs. An effective and broad influenza vaccine for pigs would greatly benefit the pork industry and contribute to public health by diminishing the risk of emerging highly pathogenic reassortants. Current inactivated protein vaccines against swine influenza produce only short-lived immunity and have no efficacy against heterologous strains. DNA vaccines are a potential alternative with advantages such as the induction of cellular and humoral immunity, inherent safety and rapid production time. We have previously developed a DNA vaccine encoding selected influenza proteins of pandemic origin and demonstrated broad protective immune responses in ferrets and pigs. In this study, we evaluated our DNA vaccine expressed by next-generation vectors. These new vectors can improve gene expression, but they are also efficiently produced on large scales and comply with regulatory guidelines by avoiding antibiotic resistance genes. In addition, a new needle-free delivery of the vaccine, convenient for mass vaccinations, was compared with intradermal needle injection followed by electroporation. We report that when our DNA vaccine is expressed by the new vectors and delivered to the skin with the needle-free device in the rabbit model, it can elicit an antibody response with the same titers as a conventional vector with intradermal electroporation. The needle-free delivery is already in use for traditional protein vaccines in pigs but should be considered as a practical alternative for the mass administration of broadly protective influenza DNA vaccines.

摘要

2009年甲型H1N1流感大流行病毒所构成的威胁凸显了研发新型甲型流感病毒疫苗的必要性,这种疫苗能够诱导产生广泛的交叉保护性免疫反应,可用于人类和猪。一种有效的、针对猪的广谱流感疫苗将极大地造福猪肉产业,并通过降低出现高致病性重配病毒的风险,为公共卫生做出贡献。目前针对猪流感的灭活蛋白疫苗仅能产生短暂的免疫力,且对异源毒株无效。DNA疫苗是一种潜在的替代方案,具有诱导细胞免疫和体液免疫、本质安全以及生产周期短等优势。我们之前研发了一种编码大流行起源的特定流感蛋白的DNA疫苗,并在雪貂和猪身上证明了其具有广泛的保护性免疫反应。在本研究中,我们评估了由新一代载体表达的DNA疫苗。这些新载体能够提高基因表达,而且它们还能大规模高效生产,并通过避免使用抗生素抗性基因来符合监管要求。此外,我们将一种便于大规模接种的新型无针疫苗接种方式与皮内针刺注射后进行电穿孔的方式进行了比较。我们报告称,在兔模型中,当我们的DNA疫苗由新载体表达并通过无针设备接种到皮肤时,它能引发与采用皮内电穿孔的传统载体相同滴度的抗体反应。无针接种方式已用于猪的传统蛋白疫苗接种,但应被视为大规模接种广谱保护性流感DNA疫苗的一种切实可行的替代方法。

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