Vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine for pigs and humans
Vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine for pigs and humans
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DOI：
10.1080/21645515.2015.1011987
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发表时间：
2015-08-03
影响因子：
4.8
通讯作者：
Fomsgaard, Anders
中科院分区：
文献类型：
--
作者：
Borggren, Marie;Nielsen, Jens;Fomsgaard, Anders
2009年大流行H1N1病毒造成的威胁强调了需要新的甲型流感病毒疫苗，以诱导广泛的交叉保护性免疫反应，供人和猪使用。一种有效和广泛的猪流感疫苗将极大地有利于猪肉行业，并通过减少出现高致病性重组体的风险来促进公众健康。目前针对猪流感的灭活蛋白疫苗只能产生短暂的免疫力，对异源毒株没有效果。DNA疫苗是一种潜在的替代疫苗，具有诱导细胞和体液免疫、固有安全性和生产时间快等优点。我们之前已经开发出一种编码大流行起源的选定流感蛋白的DNA疫苗，并在雪貂和猪身上展示了广泛的保护性免疫反应。在这项研究中，我们评估了我们的下一代载体表达的DNA疫苗。这些新载体可以改善基因表达，但它们也可以大规模高效生产，并通过避免抗生素耐药性基因来遵守监管指南。此外，一种新的无针注射疫苗，便于大规模接种，与皮内注射后电穿孔进行了比较。我们报道，当我们的DNA疫苗用新的载体表达并在兔模型中用无针装置输送到皮肤上时，它可以诱导与传统的真皮内电穿孔载体相同效价的抗体反应。这种无针头递送已经在猪的传统蛋白质疫苗中使用，但应该被视为大规模接种广泛保护性流感DNA疫苗的实用替代方案。
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.