Continued Development of a Recombinant Vaccine (RivaxTM) against Ricin Toxin

持续开发抗蓖麻毒素重组疫苗 (RivaxTM)

• 批准号: 7135886
• 负责人: ROBERT N. BREY
• 金额: $ 247.46万
• 依托单位: SOLIGENIX, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7135886
• 关键词: clinical research; toxin

DESCRIPTION (provided by applicant): Ricin is one of the most potent biological toxins known, and is classified by the CDC as a category B biothreat. Much attention has been recently focused on the potential threat of actual ricin use. Since post exposure treatment is ineffective unless administered within a narrow window of time, vaccination may be the only ways to prevent lethality and damage to tissue caused by ricin. We have developed a safe and effective vaccine (RiVax(tm)) based on a recombinant mutant that eliminates the toxicities of the A chain. A robust, high yield and scalable process for manufacturing the vaccine has been achieved. Based on preclinical safety and efficacy data, a small Phase I trial was initiated to test the tolerability and immunogenicity of the vaccine in human volunteers. We have characterized adjuvant formulations of the vaccine which will be tested next in volunteers. The vaccine has passed the initial development hurdles. The purpose of this project is to continue development of this established candidate. Specifically, we will conduct long term stability studies of the protein in solution and adsorbed to aluminum salts adjuvant. We will assess the conformational aspects of the protein and relate them to potency. Secondly, we aim to demonstrate that the vaccine will generate antibodies in rabbits and humans that can passively confer protection to rabbits after aerosol or oral ricin exposure. The use of an additional animal species other than mice will lay the groundwork for pivotal animal efficacy trials which must be conducted in place of human trials (under the FDA animal rule). Thirdly, we will conduct GLP preclinical toxicology and efficacy trials in mice and rabbits to support the clinical evaluation an adjuvanted vaccine. Our goal is to obtain several thousand doses of released vaccine that has been evaluated for stability. And finally, we intend to perform the regulatory work necessary for IND submission. This proposal represents a critical step in the further development of Rivax towards additional clinical trials and ultimately registration and marketing. There is a very real worldwide threat for the use of ricin in bioterrorism. A safe and effective FDA-approved vaccine is urgently needed for military personnel and, in the event of a domestic attack, for first responders and perhaps for the general public.

描述（由申请人提供）：蓖麻毒素是已知最有效的生物毒素之一，被美国疾病控制与预防中心列为B类生物威胁。最近，人们的注意力集中在蓖麻毒素实际使用的潜在威胁上。由于接触后的治疗除非在很短的时间内进行，否则是无效的，因此接种疫苗可能是防止由蓖麻毒素引起的致命性和组织损伤的唯一方法。我们开发了一种安全有效的疫苗（RiVax(tm)），该疫苗基于重组突变体，可消除a链的毒性。已经实现了一种稳健、高产和可扩展的疫苗生产工艺。基于临床前安全性和有效性数据，启动了一项小型I期试验，以测试疫苗在人类志愿者中的耐受性和免疫原性。我们已经确定了疫苗的佐剂配方，接下来将在志愿者中进行测试。该疫苗已经通过了最初的开发障碍。这个项目的目的是继续发展这个既定的候选人。具体来说，我们将对蛋白质在溶液和铝盐佐剂上的吸附进行长期的稳定性研究。我们将评估蛋白质的构象方面，并将它们与效力联系起来。其次，我们的目标是证明疫苗将在兔和人体内产生抗体，在气溶胶或口服蓖麻毒素暴露后被动地赋予兔保护。使用小鼠以外的其他动物品种将为关键的动物功效试验奠定基础，这些试验必须取代人体试验（根据FDA动物规则）。第三，我们将在小鼠和家兔身上进行GLP临床前毒理学和疗效试验，为佐剂疫苗的临床评价提供支持。我们的目标是获得数千剂经稳定性评估的已释放疫苗。最后，我们打算进行IND提交所需的监管工作。该提案是Rivax进一步发展的关键一步，旨在进行更多的临床试验并最终注册和销售。在生物恐怖主义中使用蓖麻毒素是一个非常现实的全球性威胁。目前迫切需要一种安全有效的经fda批准的疫苗，供军事人员使用，在发生国内袭击的情况下，供急救人员使用，也可能供公众使用。