New Generation of Anthrax Prophylaxis and Therapy

新一代炭疽预防和治疗

• 批准号: 6992509
• 负责人: Kenneth Alibek
• 金额: $ 43.28万
• 依托单位: AFG BIOSOLUTIONS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6992509
• 关键词: Bacillus anthracis; active immunization; anthrax; anthrax vaccines; antibacterial antibody; bacterial proteins; biotechnology; bioterrorism /chemical warfare; communicable disease control; immunologic substance development /preparation; laboratory mouse; laboratory rabbit; metalloendopeptidases; monoclonal antibody; nonhuman therapy evaluation; peptides; protein purification; synthetic vaccines; vaccine development; vaccine evaluation

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.

描述（由申请人提供）：这一 I 期 SBIR 申请满足了 NIAID 对高优先级生物防御产品（例如新型疫苗和治疗剂）的呼吁，以保护我们的国家免受各种生物威胁。尽管这些类型的提案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，这鼓励我们追求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肽疫苗来证明其有效性。这些制剂将基于使用在炭疽芽孢杆菌的细胞外和膜结合金属蛋白酶的活性中心中鉴定的抗原。我们决定使用这些靶点的原因如下：a) 细菌蛋白酶被认为是许多传染病的毒力因子 b) 最近的发现使得鉴定金属蛋白酶的序列基序成为可能。因此，现在可以鉴定“强毒力”金属蛋白酶的特定氨基酸序列，用作候选肽疫苗和用于免疫的肽分子，以产生用于预防和治疗炭疽的多克隆和单克隆抗体。短肽具有免疫原性，易于制造，可用于生产高纯度疫苗，并可组合为肽“混合物”，用于开发和制造多价/多表位和多剂疫苗和抗体。我们已经完成了“原理验证”研究，并建议开发一种新的炭疽疫苗和抗炭疽抗体，其具体目标如下：1）。作为多价疫苗和抗体开发候选物的肽抗原的合成、纯化和缀合； 2）。用候选肽疫苗免疫小鼠并测试由单一候选肽及其组合产生的特异性抗炭疽免疫力； 3）。针对所选肽生成特异性抗炭疽抗体并在小鼠模型中测试其保护功效。