Development and Manufacture of Adjuvants for Vaccines Targeting MDR Tuberculosis

耐多药结核病疫苗佐剂的开发和生产

• 批准号: 7617909
• 负责人: Rhea N Coler
• 金额: $ 149.16万
• 依托单位: ACCESS TO ADVANCED HEALTH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7617909
• 关键词: AS02A; Access to Information; Adjuvant; Aerosols; Agonist; Animal Model; Animals; Antigens; Applied Research; Biological Assay; Bioterrorism; Categories; Cavia; Clinical; Colorado; Contracts; Data; Development; Disease; Drug Formulations; Ensure; Evaluation; Excipients; Funding; Generations; Goals; Growth; Hand; Human; Immune response; Immune system; Immunization; In Vitro; Infection; Infectious Diseases Research; Institution; Lead; Legal patent; Licensing; Lipids; Modeling; Monkeys; Multi-Drug Resistance; Multidrug-Resistant Tuberculosis; Mus; Mycobacterium tuberculosis; National Institute of Allergy and Infectious Disease; Oils; Pharmacologic Substance; Phase I Clinical Trials; Positioning Attribute; Process; Public Sector; Publishing; Research; Research Institute; Rights; Safety; System; TLR4 gene; Testing; Toxicology; Tuberculosis Vaccines; United States National Institutes of Health; Universities; Vaccine Adjuvant; Vaccine Research; Vaccine Therapy; Vaccines; Virulent; Work; analog; aqueous; base; biodefense; cost; design; experience; human data; monophosphoryl lipid A; next generation; nonhuman primate; pre-clinical; prevent; primate development; prophylactic; research clinical testing; response; vaccine candidate; vaccine evaluation

DESCRIPTION (provided by applicant): This request for funding for applied research into rapid response vaccines and therapies for MDR-TB is a partnership between the Infectious Disease Research Institute [a not-for-profit research organization], The Vaccine Research Center, NIAID, NIH, and the TB Vaccine Testing and Research Materials Contract at Colorado State University [an academic institution]. Some Mtb antigens have shown promise in animal or in vitro systems, but have not advanced due to either lack of or poor human data. One reason is the paucity of effective adjuvants, which are molecules or compounds that stimulate specific, protective immune responses when combined with antigen. Most adjuvants are in the hands of large pharmaceutical companies. A new generation of vaccines is being developed with these adjuvants but the cost is high. Through component licensing and development of simple formulations, we will provide to the public sector safe, highly effective, low-cost alternatives to adjuvants produced by "big pharma". We will coordinate activities with the TB Vaccine Testing Contract [NIH, MAID N01-AI-40091] to prioritize Mtb antigen candidates that could benefit from IDRI's adjuvants. We will seek adjuvant rights from patent holders (Intercell, Coley Pharmaceuticals, 3M pharma division, Dainippon Sumitomo Pharmaceuticals) as needed. We have a proprietary patent position on the adjuvant use of glucopyranosil lipid adjuvant ([GLA]; an MPL analogue [Monophosphoryl Lipid A, referred to as MPL]). Our industrial experience will enable us to develop a new generation of effective adjuvant formulations designed to induce the optimal immune response. Development work will emphasize extensive characterization of safety, immune responses and protection in mice, guinea pigs and non-human primates, development of processes that can be transferred and that use materials of non-animal origin, and manufacture/release of adjuvant formulations for clinical testing with priority Mtb antigens. The selection process will emphasis both pre- and post-infection immunization as criteria for prioritization. The selected adjuvant candidate will be subjected to process development, potency and stability assays. By the end of the funding period, we will have defined and developed a new generation adjuvant, collected data for MDR-TB, and evaluated safety of the adjuvant with a GLP toxicology study. We will ensure availability of potent, highly effective adjuvants to facilitate the development of not only effective biodefense vaccines against a category C agent, MDR-TB, but also for the use of the public research sector.

说明（由申请人提供）：这项针对耐多药结核病快速反应疫苗和疗法的应用研究的资助请求是传染病研究所（非营利性研究组织）、疫苗研究中心、NIAID、NIH 和科罗拉多州立大学结核病疫苗测试和研究材料合同部（学术机构）之间的合作伙伴关系。一些 Mtb 抗原已在动物或体外系统中显示出前景，但由于缺乏或较差的人类数据而尚未取得进展。原因之一是缺乏有效的佐剂，佐剂是与抗原结合时刺激特异性、保护性免疫反应的分子或化合物。大多数佐剂掌握在大型制药公司手中。使用这些佐剂正在开发新一代疫苗，但成本很高。通过成分许可和简单配方的开发，我们将为公共部门提供“大型制药公司”生产的佐剂的安全、高效、低成本的替代品。我们将与结核病疫苗测试合同 [NIH，MAID N01-AI-40091] 协调活动，优先考虑可受益于 IDRI 佐剂的 Mtb 候选抗原。我们将根据需要向专利持有者（Intercell、Coley Pharmaceuticals、3M Pharma Division、Dainippon Sumitomo Pharmaceuticals）寻求辅助权。我们对吡喃葡萄糖脂质佐剂（[GLA]；一种MPL类似物[单磷酰脂质A，简称MPL]）的佐剂用途拥有专有专利地位。我们的工业经验将使我们能够开发新一代有效的佐剂配方，旨在诱导最佳的免疫反应。开发工作将重点强调小鼠、豚鼠和非人类灵长类动物的安全性、免疫反应和保护的广泛表征，开发可转移和使用非动物来源材料的工艺，以及制造/释放用于优先 Mtb 抗原临床测试的佐剂制剂。选择过程将强调感染前和感染后免疫作为优先考虑的标准。选定的候选佐剂将接受工艺开发、效力和稳定性测定。到资助期结束时，我们将定义和开发新一代佐剂，收集耐多药结核病的数据，并通过 GLP 毒理学研究评估佐剂的安全性。我们将确保提供强效、高效的佐剂，不仅促进针对 C 类病原体耐多药结核病的有效生物防御疫苗的开发，而且也供公共研究部门使用。