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，作为生物恐怖制剂构成严重威胁。目前的炭疽疫苗使用针头注射，需要反复免疫以产生保护作用，并需要经常加强免疫以保持免疫力，因此对这种罕见疾病进行大规模免疫是不切实际的。为了防止生物恐怖威胁，理想的炭疽疫苗应具有以下理想特征：1)立即产生保护，以便用作紧急预防措施；2)通过适用于大规模免疫的单一、简单的免疫程序产生持久的免疫。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)肺部快速的先天反应，可能会立即提供对吸入性炭疽的保护，2)稳定的记忆B细胞和T细胞可能会提供持久的免疫。该申请的目的是开发适合和安全的新型减毒菌株，以进一步开发和临床测试我们的新型疫苗平台。这项I期STTR申请的具体目的是：1)构建新的减毒菌株并测试其毒力和作为高度减毒疫苗菌株的潜力；2)测试我们的新疫苗株在肺部诱导快速先天反应的能力，并产生高水平的抗体和持久的T细胞记忆。在I期研究结束时，我们希望鉴定出新的减毒疫苗毒株，这种毒株是严重减毒但具有高度免疫原性的。这将为II期研究奠定基础，在II期研究中，我们将在小动物模型和非人灵长类动物中测试这些新的减毒菌株，以诱导对完全毒力炭疽芽胞杆菌的保护性免疫。结合新的减毒菌株和新的疫苗平台，我们的最终目标是开发一种适合大规模免疫的疫苗接种策略，以诱导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.