New attenuated anthrax vaccine

描述（由申请人提供）：炭疽是一种罕见但致命的疾病，作为生物恐怖剂构成严重威胁。目前的炭疽疫苗使用针头注射，需要反复免疫以诱导保护和频繁加强以维持免疫力，因此对于这种罕见疾病的大规模免疫是不切实际的。为了保护免受生物恐怖威胁，理想的炭疽疫苗应具有以下所需的特征：1）诱导立即保护，使其可用作紧急预防，以及2）通过适合于大规模免疫的单一简单免疫程序诱导持久免疫。我们已经测试了一种新的疫苗平台，我们的初步结果表明，这种免疫策略诱导1）肺中的快速先天反应，可以立即提供针对吸入性炭疽的保护，以及2）稳定的记忆B和T细胞，可能提供持久的免疫力。本申请的目的是开发新的减毒菌株，适用于我们新型疫苗平台的进一步开发和临床试验。本次I期STTR申请的具体目的是：1）构建新的减毒株，并测试其毒力和作为高度减毒疫苗株的潜力; 2）测试我们的新疫苗株诱导肺部快速先天性应答的能力，以及产生高水平抗体和持久T细胞记忆的能力。在这项I期研究结束时，我们希望鉴定出新的减毒疫苗株，这些疫苗株是严重减毒的，但具有高度免疫原性。这将为II期研究奠定基础，在该研究中，我们将测试这些新的减毒株诱导针对完全强毒B的保护性免疫。在小动物模型和非人类灵长类动物中的炭疽病。结合新的减毒株和新的疫苗平台，我们的最终目标是开发适合大规模免疫的疫苗接种策略，以诱导针对肺炭疽的即时和长期保护性免疫。

DESCRIPTION (provided by applicant): Anthrax is a rare, but deadly disease and poses a serious threat as a bioterror agent. The current anthrax vaccine uses needle injection and requires repeated immunizations for inducing protection and frequent boosts for maintaining immunity, thus making it impractical for mass immunization against this rare disease. To protect against bioterror threats, an ideal anthrax vaccine would have the following desired features: 1) inducing immediate protection so that it can be used as an emergent prophylaxis, and 2) inducing long-lasting immunity by a single, simple immunization procedure suitable for mass immunization. We have tested a novel vaccine platform and our preliminary results indicate that this immunization strategy induce 1) a rapid innate response in the lung that may confer immediate protection against inhalational anthrax, and 2) stable memory B and T cells that will likely provide long-lasting immunity. The objective of this application is to develop new attenuated strains suitable and safe for further development and clinical testing of our novel vaccine platform. The specific aims of this Phase I STTR application are: 1) to construct new attenuated strains and test their virulence and potential as highly attenuated vaccine strains; 2) to test the ability of our new vaccine strains to induce the rapid innate response in the lung and to generate high levels of antibodies and long-lasting T cell memory. At the end of this Phase I study, we hope to identify new attenuated vaccine strains that are severely attenuated yet highly immunogenic. This will set the stage for the Phase II study in which we will test these new attenuated strains for inducing protective immunity against fully virulent B. anthracis in small animal models and non-human primates. With the combination of new attenuated strains and a novel vaccine platform, our ultimate goal is to develop a vaccination strategy suitable for mass immunization to induce immediate and long-term protective immunity against pulmonary anthrax.