DEVELOPMENT OF A LIPOSOMAL PNEUMOCOCCAL VACCINE FOR CLINICAL READINESS

开发用于临床准备的脂质体肺炎球菌疫苗

基本信息

  • 批准号:
    10010219
  • 负责人:
  • 金额:
    $ 71.6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-04-24 至 2023-03-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY The illnesses caused by Streptococcus pneumoniae’s transition from carriage to disease result in a mortality rate between approximately 3-10% in adults and 12-25% in elderly patients in the United States. Furthermore, pneumococcal disease devastates resource-poor countries, causing an estimated 476,000 people to succumb to pneumococcal infection annually (~32% of vaccine-preventable deaths in children below age five). The most effective vaccines, polysaccharide protein conjugates, require a complicated process of collecting polysaccharide antigens from pneumococci serotypes and conjugating them to a protein adjuvant. Abcombi Biosciences has developed a pneumococcal vaccine using liposomal encapsulation of polysaccharides (LEPS), which has demonstrated conjugate-like efficacy against 70+ serotypes of S. pneumoniae via animal challenge models and opsonophagocytosis activity (OPA). Since receiving our prior Phase I SBIR award, Abcombi Biosciences has completed all proposed milestones to address concerns regarding the risk for potential negative side effects associated with the LEPS vaccine’s formulation. Completion of this work has led to the development of a second generation LEPS vaccine. The enclosed Direct Phase II SBIR proposal outlines the remaining preclinical studies necessary to reach our next major milestone, a pre-IND meeting with the FDA. The completion of these studies will serve to address important considerations of the FDA regarding vaccine manufacturing and characterization (i.e., chemistry manufacturing and controls, CMC) and efficacy (i.e., the animal rule). Briefly, these studies will involve the completion the following key developmental steps: 1) optimization of our encapsulation process for all pneumococcal capsular polysaccharides (CPSs), 2) finalization of polysaccharide dosage, 3) evaluation of vaccine stability, and 4) a repeated-dose toxicology study in mice and rabbits. Optimization of our polysaccharide encapsulation process will be achieved by systematically varying our process conditions across all 24 polysaccharides to ensure efficient and consistent encapsulation for each antigen. Upon optimizing this process, we will then identify the optimal dosage of polysaccharide by measuring antibody titers and OPA assay performance to determine the dosage of each polysaccharide required for sufficient immunogenicity. We will then characterize the LEPS vaccine stability by evaluating protein pH and thermal stability as well as the integrity of the liposomes when stored over 12 months. Lastly, we will evaluate the vaccine for toxicity in a repeated dose study in mice and rabbits. Throughout the duration of this study, serum will be collected to evaluate organ toxicity and quantify antibody titers. In addition, post-mortem tissue samples will be extracted to visualize histopathology. Successful completion of this work will prepare our vaccine candidate for a pre-IND meeting with the FDA and ensure a smooth transition into clinical trials.
项目摘要 由肺炎链球菌从携带转变为疾病引起的疾病导致 在美国,成人的死亡率约为3-10%,老年患者的死亡率约为12-25%。 此外,肺炎球菌疾病使资源贫乏的国家陷入困境,估计造成476,000人死亡。 每年死于肺炎球菌感染的人(约32%的儿童可预防的死亡, 5岁)。最有效的疫苗,多糖蛋白结合物,需要一个复杂的过程, 从肺炎球菌血清型中收集多糖抗原并将它们与蛋白佐剂结合。 Abcombi Biosciences开发了一种肺炎球菌疫苗, 多糖(LEPS),其已证明对70+血清型的S. 肺炎通过动物攻击模型和调理吞噬活性(OPA)。自从收到我们的前任 第一阶段SBIR奖,Abcombi Biosciences已经完成了所有拟议的里程碑,以解决问题 关于LEPS疫苗配方相关的潜在负面副作用的风险。 这项工作的完成导致了第二代LEPS疫苗的开发。封闭 直接II期SBIR提案概述了达到我们下一个主要目标所需的剩余临床前研究 里程碑,与FDA的IND前会议。这些研究的完成将有助于解决 FDA关于疫苗生产和表征的重要考虑(即,化学 制造和控制,CMC)和功效(即,动物规则)。简而言之,这些研究将涉及 完成以下关键发展步骤:1)优化我们的封装工艺, 肺炎球菌荚膜多糖(CPS),2)最终确定多糖剂量,3)评价 疫苗稳定性,和4)在小鼠和兔中的重复剂量毒理学研究。优化我们的 通过系统地改变我们的工艺条件, 以确保对每种抗原的有效和一致的包封。后 优化此工艺,通过抗体测定确定多糖的最佳用量, 滴度和OPA测定性能,以确定足够的多糖所需的每种多糖的剂量。 免疫原性然后,我们将通过评价蛋白质pH和热稳定性来表征LEPS疫苗的稳定性。 稳定性以及当储存超过12个月时脂质体的完整性。最后,我们将评估 在小鼠和家兔中进行的重复剂量研究中,在整个过程中, 在本研究中,将收集血清以评价器官毒性并定量抗体滴度。此外,死后 将提取组织样本以观察组织病理学。这项工作的顺利完成将 为我们的候选疫苗与FDA的IND前会议做好准备,并确保顺利过渡到 临床试验

项目成果

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Charles Houston Jones其他文献

Charles Houston Jones的其他文献

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{{ truncateString('Charles Houston Jones', 18)}}的其他基金

DEVELOPMENT OF A LIPOSOMAL PNEUMOCOCCAL VACCINE FOR CLINICAL READINESS
开发用于临床准备的脂质体肺炎球菌疫苗
  • 批准号:
    10373030
  • 财政年份:
    2020
  • 资助金额:
    $ 71.6万
  • 项目类别:
Therapy for drug resistant influenza strains by nucleic acid targeting of respiratory airways
核酸靶向呼吸道治疗耐药流感病毒株
  • 批准号:
    9406008
  • 财政年份:
    2016
  • 资助金额:
    $ 71.6万
  • 项目类别:

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