New Generation of Anthrax Prophylaxis and Therapy

描述(由申请人提供)：此第一阶段SBIR申请针对NIAID对高优先级生物防御产品的呼吁，如新型疫苗和治疗药物，以保护我们的国家免受各种生物制剂的伤害。虽然这些类型的建议不需要大量的初步数据，但我们已经进行了大量的初步实验工作，这鼓励我们寻求一种创新和革命性的方法来开发抗炭疽预防和治疗制剂。在短短12个月的研究中，我们计划通过开发新型多价抗炭疽抗体和多价炭疽多肽疫苗来证明其有效性。这些准备工作将基于炭疽芽孢杆菌胞外和膜结合金属蛋白酶活性中心中确定的抗原的使用。我们决定使用这些靶标是因为以下几个原因：a)细菌蛋白酶被认为是许多传染病的毒力因子；b)最近的发现使识别金属蛋白酶的序列基序成为可能。因此，现在可以鉴定用于作为多肽疫苗候选者和作为免疫的多肽分子以产生用于预防和治疗炭疽的多克隆和单克隆抗体的毒力较强的金属蛋白酶的特定氨基酸序列。已证明，短肽具有免疫原性，易于制造，可用于生产高纯度的疫苗，并可组合成用于开发和制造多价/多表位和多试剂疫苗和抗体的多肽的“鸡尾酒”。我们已经完成了我们的原则性证明研究，并建议开发一种新的炭疽疫苗和抗炭疽抗体，具体目标如下：1)。多价疫苗和抗体开发的候选多肽抗原的合成、纯化和偶联；用候选多肽疫苗免疫小鼠，并检测由单一候选多肽及其组合产生的特异性抗炭疽免疫；产生针对所选多肽的特异性抗炭疽抗体，并在小鼠模型中测试其保护效果。

DESCRIPTION (provided by applicant): This Phase I SBIR application addresses the NIAID call for high priority biodefense products such as novel vaccines and therapeutics to protect our nation against various biothreat agents. Although these types of proposals do not require a significant amount of preliminary data, we have already performed substantial preliminary experimental work that encourages us to pursue an innovative and revolutionary approach for developing anti-anthrax preventive and therapeutic preparations. Within a short 12-month study, we plan to prove its effectiveness by developing novel multivalent anti-anthrax antibodies and multivalent anthrax peptide vaccine. These preparations will be based on the use of antigens identified in the active centers of extracellular and membrane-bound metalloproteinases of Bacillus anthracis. We decided to use these targets for the following reasons: a) Bacterial proteinases are recognized as virulence factors in a number of infectious diseases b) Recent discoveries have made it possible to identify sequence motifs of metalloproteinases. Consequently, it is now possible to identify specific amino acid sequences of "virulent" metalloproteinases for use as peptide vaccine candidates and as peptide molecules for immunization to generate both polyclonal and monoclonal antibodies for the prophylaxis and treatment of anthrax c) It has been proven that short peptides are immunogenic, can be easily manufactured, may be used for production of highly pure vaccines and can be combined as "cocktails" of peptides for the development and manufacture of multivalent/multiepitope and multiagent vaccines and antibodies. We have already finished our "proof-of principle" study and propose to develop a new anthrax vaccine and anti-anthrax antibodies with the following specific aims: 1). Synthesis, purification and conjugation of peptide antigens as candidates for multivalent vaccine and antibody development; 2). Immunization of mice with the peptide vaccine candidates and testing of specific anti-anthrax immunity generated by a single peptide candidate and a combination thereof; 3). Generation of specific anti-anthrax antibodies against the selected peptides and testing their protective efficacy in the murine model.