Immuno-enhancement of skin patch anthrax vaccination

描述(申请人提供)：在生物恐怖主义之后，炭疽病已成为公众真正关注的问题。炭疽病被疾控中心列为A类生物疾病。吸入炭疽孢子可导致快速致命出血而死亡。由于炭疽气雾剂无臭、看不见、容易传播，因此保护人们免受感染的最有效方法是接种疫苗。无复制能力重组腺病毒是一种非侵入性、高效、安全、经济的非侵入性免疫接种技术。最近，华信公司研制出了编码炭疽保护性抗原(PA)的重组腺病毒，可用于皮肤炭疽疫苗的接种。诱导保护性反应的一个重要问题是皮肤斑贴疫苗的效果，这取决于免疫反应的发展。皮肤中的树突状细胞(DC)在诱导对疫苗抗原的免疫反应中起着重要作用。皮肤接种疫苗诱导DC从皮肤向脾和区域淋巴结迁移，在那里DC将疫苗抗原呈递给淋巴细胞并诱导免疫反应。我们最近的研究表明，Slit2是一种在皮肤中表达的可溶性蛋白，可以抑制DC向皮肤外的迁移。应用slit2的可溶性受体Robo可以增加DC的迁移，并增强对皮肤上抗原刺激的免疫反应。这一建议的假设是，应用可溶性Robo可以提高皮肤贴剂Antrax疫苗的效果。这项第一阶段的研究将首先调查炭疽病。其次，将检测编码可溶性Robo的重组腺病毒对炭疽疫苗效力的影响。最后，这项研究将确定Robo提高皮肤贴片炭疽疫苗效力的机制。Robon和炭疽疫苗都将在不注射针头的情况下应用于皮肤，完成这项建议的研究还将提供一个加强皮肤贴片炭疽疫苗接种的方案。最终，这一方案也可能应用于针对其他病原体和肿瘤抗原的皮肤贴片疫苗。

DESCRIPTION (provided by applicant): In the wake of bio-terrorism, anthrax has become a real concern for public. Anthrax is listed as a category A biological disease by the CDC. Inhalation of anthrax spores can result in death due to rapid fatal hemorrhage. Since anthrax aerosol is odorless, invisible and easily spread, the most effective way to protect people from infection is vaccination. Skin patch vaccination with replication-incompetent recombinant adenovirus which is genetically engineered to encode pathogen antigens is a non-invasive, effective, safe and economical technology for vaccination. Recently, Vaxin, Inc. has generated recombinant adenovirus encoding anthrax protective antigen (PA), which can be used for skin patch anthrax vaccination. An important issue for the induction of protective responses is the efficacy of skin patch vaccination, which is dependent on the development of immune responses. Dendritic cells (DC) in the skin play a major role in the induction of immune responses to vaccinated antigens. Cutaneous application of vaccines induces DC migration from the skin to the spleen and regional lymph node where DC present vaccine antigens to lymphocytes and induce immune responses. Our recent studies have demonstrated that Slit2, a soluble protein expressed in the skin, inhibits DC migration out of the skin. Application of a soluble receptor for Slit2, Robo, can increase DC migration and enhance immune responses to antigen stimulation on the skin. The hypothesis of this proposal is that application of soluble Robo can enhance the efficacy of skin patch antrax vaccination. This Phase I study will first investigate against anthrax. Second, the effect of recombinant adenovirus encoding the soluble Robo on the efficacy of the anthrax vaccine will be examined. Finally, the study will determine the mechanism by which Robo increases the efficacy of skin-patch anthrax vaccination. Both RoboN and the anthrax vaccine will be applied to the skin without needle injection, completion of the studies in this proposal will also provide a protocol for enhancing the skin-patch anthrax vaccination. Ultimately, this protocol may also be applied for skin-patch vaccines to other pathogens and tumor antigens.