Prophylactic Anthrax Toxin Vaccine

预防性炭疽毒素疫苗

• 批准号: 6643978
• 负责人: PETER M. HOBART
• 金额: $ 192.37万
• 依托单位: VICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6643978
• 关键词: Bacillus anthracis; Macaca fascicularis; active immunization; anthrax; anthrax vaccines; bacterial toxins; bioterrorism /chemical warfare; clinical research; clinical trial phase I; drug screening /evaluation; gene delivery system; human subject; human therapy evaluation; laboratory mouse; laboratory rabbit; lethal genes; nonhuman therapy evaluation; patient oriented research; plasmids; spores; vaccine development; vaccine evaluation; vector vaccine

DESCRIPTION (provided by applicant): Vical Inc. seeks SBIR Phase II funding to develop and produce a licensable prophylactic anthrax vaccine. This project will move on an accelerated but realistic timeline with plans for human clinical trials to begin in September 2003. Although many candidate vaccines are being studied for anthrax prevention or post-exposure prophylaxis, the Vical approach has a number of advantages. First, we are finishing the preclinical work needed, and will approach the FDA for a pre-IND meeting to be held in March 2003. Second, DNA vaccines studied to date have been very safe in humans. Third, these vaccines have the potential for long-term stability and storage. Fourth, we are achieving antibody titers that are consistent with the levels needed for protection. Fifth, our vaccine may induce greater T cell help and memory than planned recombinant protein vaccines. Sixth, the Vical vaccine will focus on two gene products (PA plus LF) rather than PA alone, which may induce broader protection. The vaccine development plan will follow a logical series of experiments in mice, rabbits, cynomologus monkeys, and humans. In Aim 1 we will determine the final vaccine formulation that will proceed to human trials. Present experiments funded by a Phase I STTR will provide the data for choosing a final 2 formulations and constructs from among our many candidate vaccines. Cynomologus immunogenicity studies will then be performed with these candidates to determine which combination induces the optimal antibody titers. Rabbit studies will also be performed to better define the length of protection induced by our vaccines. In Aim 2 we will move a final single formulation forward into human clinical trials. This will be accomplished by conducting the appropriate quality control, toxicology and safety studies of the GMP produced vaccine, and by filing the appropriate regulatory paperwork for an IND with the FDA. The human clinical phase I trial will be a dose-ranging, open-label safety study. In Aim 3 we will select a dose from our phase I studies needed to perform a sufficiently powered clinical trial to establish vaccine safety in humans. We will also conduct the necessary studies in non-human primates to demonstrate protection from an aerosolized B. anthracis challenge using the same vaccine studied in humans. We will also collect sufficient antibody through plasmapheresis of the human subjects during our clinical trials to be able to perform passive transfer experiments in the cynomologus monkeys. These final studies will better define the role of antibody in the expected immunity to challenge.

描述（由申请人提供）：Vical Inc.寻求SBIR第二阶段资金来开发和生产可获得许可的预防性炭疽疫苗。 该项目将在加速但现实的时间轴上进行，计划于2003年9月开始进行人体临床试验。 虽然许多候选疫苗正在研究炭疽预防或暴露后预防，Vical方法有许多优点。 首先，我们正在完成所需的临床前工作，并将与FDA联系，于2003年3月举行IND前会议。 其次，迄今为止研究的DNA疫苗在人类中非常安全。 第三，这些疫苗具有长期稳定性和储存的潜力。 第四，我们正在实现与保护所需水平一致的抗体滴度。 第五，我们的疫苗可能比计划中的重组蛋白疫苗诱导更大的T细胞帮助和记忆。 第六，Vical疫苗将关注两种基因产物（PA加LF），而不是单独的PA，这可能会诱导更广泛的保护。 疫苗开发计划将遵循在小鼠、兔子、食蟹猴和人类中进行的一系列合乎逻辑的实验。 在目标1中，我们将确定将进行人体试验的最终疫苗配方。 目前由I期STTR资助的实验将提供从我们的许多候选疫苗中选择最终2种制剂和构建体的数据。 然后将使用这些候选物进行食蟹猴免疫原性研究，以确定哪种组合诱导最佳抗体滴度。 还将进行兔子研究，以更好地确定我们的疫苗诱导的保护期。 在目标2中，我们将把最终的单一配方推进人体临床试验。 这将通过对GMP生产的疫苗进行适当的质量控制、毒理学和安全性研究，并向FDA提交IND的适当监管文件来实现。 人体临床I期试验将是一项剂量范围、开放标签安全性研究。 在目标3中，我们将从我们的I期研究中选择一种剂量，以进行足够有力的临床试验来确定疫苗在人体中的安全性。 我们还将在非人类灵长类动物中进行必要的研究，以证明对雾化B的保护作用。炭疽菌攻击使用相同的疫苗在人类中研究。 我们还将在临床试验期间通过对人类受试者进行血浆置换收集足够的抗体，以便能够在食蟹猴中进行被动转移实验。 这些最终研究将更好地确定抗体在预期攻毒免疫中的作用。