Preclinical Assessment of a Multi-Head Electroporation Device for Delivery of Bio

用于生物递送的多头电穿孔装置的临床前评估

• 批准号: 8649026
• 负责人: Connie Schmaljohn
• 金额: $ 78.59万
• 依托单位: GENEVA FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8649026
• 关键词: Adjuvant; Affect; Africa; Area; Arenavirus; Arenavirus Infections; Biological; Biological Assay; Bioterrorism; Categories; Cavia; Centers for Disease Control and Prevention (U.S.); Clinical Research; Codon Nucleotides; Cold Chains; Combined Vaccines; DNA; DNA Vaccines; Dermal; Development; Devices; Disease model; Dose; Electroporation; Emerging Communicable Diseases; Engineering; Genetic Engineering; Goals; Head; Immune; Immune response; Immunity; Lassa virus; Licensing; Mass Vaccinations; Medical; Methods; Molecular; Patients; Plasmids; Primate Diseases; Public Health; Safety; Site; Skin; Technology; Testing; Therapeutic; Vaccination; Vaccines; Validation; Viral Hemorrhagic Fevers; base; biodefense; biothreat; cytokine; design; immunogenicity; improved; nonhuman primate; novel; pathogen; pre-clinical; prototype; public health relevance; therapeutic vaccine; vaccine delivery; vaccine development; vaccine efficacy; viral DNA

DESCRIPTION (provided by applicant): DNA-based vaccines have an excellent safety record, are inherently stable, are simple to create, can be manufactured rapidly and do not require cold-chain storage, making this technology attractive for use against bioterrorism threats, emerging infectious diseases or genetically engineered pathogens. Despite these attributes, DNA vaccines have not achieved routine usage in large part due to poor immunogenicity related to ineffective delivery methods. We previously developed and tested a DNA vaccine for the Category A biothreat Lassa virus (LASV). This arenavirus is endemic in West Africa where it infects hundreds of thousands of people each year and can cause a highly lethal hemorrhagic fever. We showed that a codon optimized DNA vaccine for LASV delivered by intradermal electroporation (ID-EP) is completely protective against LASV challenge in both guinea pig and nonhuman primate disease models. Although these results are highly encouraging and the ID-EP technology is a very tolerable delivery method from a patient perspective, improvements are still needed to make the technology suitable for mass vaccination. In this application, we describe technological improvements that we expect will result in better vaccine efficacy and ease of use as compared to our existing delivery platform. We propose to develop novel devices with dual depth and/or multiple EP arrays that can target spatially separated skin areas. We will test the devices using the LASV DNA vaccine by itself or delivered in combination with cytokine adjuvants or with DNA vaccines for two additional arenaviruses. Our main goals are: 1) Develop automated, multi-head ID/EP devices able to deliver multiple products to discreet sites simultaneously and/or target different compartments of the skin; 2) Determine the affect of co-administering the LASV DNA vaccine with plasmids encoding molecular adjuvants delivered with the novel ID-EP devices; and, 3) Assess the ability of the multi-array ID-EP devices to effectively deliver multiagent arenavirus vaccines. Accomplishment of these goals will not only fill a critical biodefense and public health gap with respect to medical countermeasures against LASV, but will also advance the DNA vaccine field in general by providing a highly tolerable mass vaccination method amenable to multiagent vaccine delivery.

描述(申请人提供)：基于DNA的疫苗具有出色的安全记录、固有的稳定性、简单的制造、可快速制造且不需要冷链储存，使这项技术在对抗生物恐怖主义威胁、新出现的传染病或基因工程病原体方面具有吸引力。尽管有这些属性，DNA疫苗尚未实现常规使用，很大程度上是由于免疫原性较差，与无效的递送方法有关。我们之前开发并测试了一种针对A类生物毒株拉萨病毒(LASV)的DNA疫苗。这种阿拉伯病毒在西非流行，每年感染数十万人，并可导致高度致命的出血热。在豚鼠和非人类灵长类动物疾病模型中，我们证明了通过皮内电穿孔(ID-EP)递送的LASV密码子优化的DNA疫苗对LASV攻击具有完全的保护作用。尽管这些结果非常令人鼓舞，而且从患者的角度来看，ID-EP技术是一种非常可容忍的递送方法，但仍需要改进，以使该技术适合大规模疫苗接种。 在本申请中，我们描述了与我们现有的交付平台相比，我们预计将产生更好的疫苗效力和易用性的技术改进。我们建议开发具有双深度和/或多个EP阵列的新型设备，可以针对空间分离的皮肤区域。我们将使用LASV DNA疫苗本身或与细胞因子佐剂或针对另外两种Arena病毒的DNA疫苗一起交付来测试这些设备。我们的主要目标是：1)开发自动化的多头ID/EP设备，能够将多种产品同时输送到谨慎的部位和/或靶向皮肤的不同隔室；2)确定LASV DNA疫苗与编码分子佐剂的质粒与新型ID-EP设备一起输送的影响；以及3)评估多阵列ID-EP设备有效输送多代理ArenaVirus疫苗的能力。这些目标的实现不仅将填补针对LASV的医学对策方面的关键生物防御和公共卫生空白，而且还将通过提供一种高度耐受的、可接受多剂疫苗递送的大规模疫苗接种方法，推动DNA疫苗领域的整体发展。