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通过电穿孔传递线性表达盒的甲型流感疫苗在小鼠模型中提供了针对挑战的完全保护。

Influenza A vaccines using linear expression cassettes delivered via electroporation afford full protection against challenge in a mouse model.

机构信息

Inovio Pharmaceuticals, 1787 Sentry Parkway West, Blue Bell, PA 19422, USA.

出版信息

Vaccine. 2012 Nov 6;30(48):6946-54. doi: 10.1016/j.vaccine.2012.02.071. Epub 2012 Mar 8.

Abstract

Alternative DNA vaccine constructs such as fully synthetic linear expressing cassettes (LECs) offer the advantage of accelerated manufacturing techniques as well as the lack of both antibiotic resistance genes and bacterial contaminants. The speed of manufacture makes LEC technology a possible future vaccination strategy for pandemic influenza outbreaks. Previously, we reported on a novel concept of DNA delivery to dermal tissue by a minimally invasive electroporation (EP) surface device powered using low voltage parameters. This device allows electroporation without penetration of electrodes into the skin. In addition to enhancing the delivery of traditional plasmid DNA vaccines, this device may also offer a safe, tolerable and efficient method to administer LECs. To assess immunogenicity and efficacy of EP-enhanced LEC delivery in mice, we designed and tested two influenza antigens in the form of LEC constructs delivered using the newly developed surface dermal EP device. Strong CTL and antibody responses were induced by the LEC versions of the DNA vaccine. When challenged with A/Canada/AB/RV1532/2009 viruses, mice immunized with LEC encoding the M2 and NP antigens recovered faster than naïve or mice immunized ID without EP. Mice immunized with equal-molar doses of LEC encoding the M2 and NP antigens demonstrated 100% survival following a lethal (100× LD50) challenge of the heterologuos and highly pathogenic H5N1 influenza virus (A/Vietnam/1203/04). These results suggest that influenza DNA vaccines based on LEC technology combined with the surface delivery platform are capable of fully protecting mice in a lethal challenge and the LEC based DNA constructs may serve as viable vaccine candidates.

摘要

替代 DNA 疫苗构建体,如完全合成的线性表达盒(LEC),具有加速制造技术的优势,并且缺乏抗生素抗性基因和细菌污染物。制造速度使 LEC 技术成为大流行性流感爆发的未来潜在疫苗接种策略。此前,我们报道了一种通过使用低电压参数供电的微创电穿孔(EP)表面装置将 DNA 递送至真皮组织的新型概念。该设备允许在不将电极穿透皮肤的情况下进行电穿孔。除了增强传统质粒 DNA 疫苗的递送外,该设备还可能提供一种安全、耐受和有效的方法来管理 LEC。为了评估经 EP 增强的 LEC 递送至小鼠中的免疫原性和功效,我们设计并测试了两种以 LEC 构建体形式递送至新开发的表面真皮 EP 设备的流感抗原。LEC 版本的 DNA 疫苗诱导了强烈的 CTL 和抗体反应。当用 A/Canada/AB/RV1532/2009 病毒进行攻毒时,用编码 M2 和 NP 抗原的 LEC 免疫的小鼠比未免疫或未经 ID 电穿孔免疫的小鼠恢复得更快。用编码 M2 和 NP 抗原的等摩尔剂量的 LEC 免疫的小鼠在接受致死性(100×LD50)挑战异源和高致病性 H5N1 流感病毒(A/Vietnam/1203/04)后,100%存活。这些结果表明,基于 LEC 技术与表面递药平台相结合的流感 DNA 疫苗能够完全保护小鼠免受致死性挑战,并且基于 LEC 的 DNA 构建体可能成为可行的疫苗候选物。

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