CONTINUED DEVELOPMENT OF RIVAX VACCINE FOR RICIN

RIVAX 蓖麻毒素疫苗的持续开发

基本信息

批准号：
7958708
负责人：
CHAD J. ROY
金额：
$ 5.8万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-01 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7958708
关键词：
Adjuvant Aerosols Aluminum Animals Antibodies Attention Biological Bioterrorism Categories Centers for Disease Control and Prevention (U.S.)Clinical Trials Computer Retrieval of Information on Scientific Projects Database Data Development Dose Evaluation Event FDA approved Funding General Population Goals Grant Human Human Volunteers Institution Military Personnel Mus Oral Oryctolagus cuniculus Phase Phase I Clinical Trials Primates Proteins Recombinants Research Research Personnel Resources Ricin Ricin Vaccine Salts Solutions Source Testing Time Tissues Toxic effect Toxicology Toxin United States National Institutes of Health Vaccination Vaccines Work animal efficacy animal rule base biothreat efficacy trial emergency service responder immunogenicity manufacturing process mutant nonhuman primate pre-clinical preclinical safety prevent research clinical testing vaccine candidate

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. a vaccine (RiVaxtm) has been developed 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. 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 nonhuman primates and humans that can passively confer protection to nonhuman primates 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 project represents a critical step in the further development of Rivax towards additional clinical trials and ultimately registration. 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. Ongoing research at the TNPRC includes evaluation of the ricin vaccine candidate in nonhuman primates. We are presently engaged in a nonhuman primate study (n=18) to determine immunogenicity and efficacy against aerosol ricin challenge. To date, the first phase of this study is underway; animals have been immunized with the vaccine candidate and await aerosol challenge.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。子项目及研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以在其他 CRISP 条目中表示。列出的机构是中心，不一定是研究者的机构。蓖麻毒素是已知最有效的生物毒素之一，被 CDC 归类为 B 类生物威胁。最近，人们的注意力集中在实际使用蓖麻毒素的潜在威胁上。由于除非在很短的时间范围内进行，否则暴露后治疗是无效的，因此疫苗接种可能是防止蓖麻毒素引起的致死和组织损伤的唯一方法。基于消除 A 链毒性的重组突变体已开发出疫苗 (RiVaxtm)。已经实现了稳健、高产量和可扩展的疫苗生产工艺。根据临床前安全性和有效性数据，启动了一项小型一期试验，以测试疫苗在人类志愿者中的耐受性和免疫原性。该项目的目的是继续开发这个已确定的候选者。具体来说，我们将对溶液中的蛋白质和吸附到铝盐佐剂上的蛋白质进行长期稳定性研究。我们将评估蛋白质的构象方面并将其与效力联系起来。其次，我们的目标是证明该疫苗将在非人类灵长类动物和人类体内产生抗体，这些抗体可以在接触气溶胶或口服蓖麻毒素后被动地为非人类灵长类动物提供保护。使用小鼠以外的其他动物物种将为关键的动物功效试验奠定基础，这些试验必须代替人体试验（根据 FDA 动物规则）。第三，我们将在小鼠和兔子中进行GLP临床前毒理学和功效试验，以支持佐剂疫苗的临床评价。我们的目标是获得数千剂已发布的疫苗，并对其稳定性进行了评估。最后，我们打算执行 IND 提交所需的监管工作。该项目代表了 Rivax 进一步开发、迈向更多临床试验和最终注册的关键一步。在生物恐怖主义中使用蓖麻毒素确实构成了全球威胁。军事人员迫切需要一种经 FDA 批准的安全有效的疫苗，在发生国内袭击时，急救人员甚至公众也迫切需要这种疫苗。 TNPRC 正在进行的研究包括在非人类灵长类动物中评估候选蓖麻毒素疫苗。我们目前正在进行一项非人类灵长类动物研究（n=18），以确定针对气溶胶蓖麻毒素攻击的免疫原性和功效。迄今为止，这项研究的第一阶段正在进行中；动物已经用候选疫苗免疫并等待气溶胶攻击。