Immuno-Chemotherapy to Shorten TB Treatment

免疫化疗缩短结核病治疗时间

基本信息

批准号：
8647793
负责人：
Rhea N Coler
金额：
$ 30万
依托单位：
PAI LIFE SCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8647793
关键词：
Address Adjuvant Aerosols Agonist Animal Model Animals Antibiotic Resistance Antibiotic Therapy Antibiotics Antigens Attention Bacteria Cessation of life Clinical Trials Collaborations Combined Modality Therapy Communicable Diseases Complex Data Development Disease Dose Drug Resistant Tuberculosis Drug resistance Drug resistance in tuberculosis Foundations Funding Funding Agency Future Generations Goals Growth Human Immune Immune response Immune system Immunotherapeutic agent Immunotherapy In Vitro Infection Infectious Diseases Research Lead Lung Methodology Mycobacterium tuberculosis Newly Diagnosed Pharmaceutical Preparations Pharmacotherapy Phase II Clinical Trials Play Prevention therapy Public Health Publishing Regimen Relapse Research Institute Rifampin Role Shapes TLR4 gene Testing Therapeutic Time Treatment Protocols Tuberculosis Tuberculosis Vaccines Vaccination Vaccine Antigen Vaccines adaptive immunity authority base cancer immunotherapy chemotherapeutic agent chemotherapy compliance behavior design effective therapy global health improved in vivo isoniazid mortality novel novel therapeutics pandemic disease pathogen prevent programs prophylactic protective effect public health relevance resistant strain response therapeutic vaccine therapy duration transmission process tuberculosis treatment vaccine candidate

项目摘要

DESCRIPTION (provided by applicant): Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (Mtb), is an ongoing threat to public health. Globally, approximately two billion people are infected with TB, with nine million newly diagnosed cases of active TB each year causing 1.5 million deaths. Furthermore, mismanagement or inappropriate treatments for TB infections can result in the development of drug resistant TB cases, for which treatments are difficult and expensive. Drug-resistant strains of Mtb are not treatable with frontline therapy and require 12-24 months of complex second and third line antibiotics. In addition, TDR (totally drug resistant) strains exist which cannot be treated with any available antibiotics. The current proposal is designed to develop a novel synergistic combination chemo-immunotherapeutic regimen for the treatment of infections caused by Mtb, including multi-, extremely- and totally- drug resistant strains. An effective treatment that reduces bacterial loads and shortens therapy to less than six months would play an important role in dramatically reducing the impact of this pathogen. This application is an extension of our systematic and methodical approach towards developing vaccines for TB. Over the last twenty years, we have applied this strategy towards developing M72/AS01E (currently in Phase II clinical trials) and ID93/GLA-SE into viable vaccine candidates. At present, to our knowledge, ID93/GLA-SE is the sole TB vaccine candidate that has been tested for prevention and therapy in multiple animal models of TB. Our candidate vaccine has three protective effects: significantly reduces pulmonary bacterial loads, reduces disseminated Mtb infection after aerosol challenge, and post-exposure immunotherapeutic protection. Funding this application will help our continuing efforts to develop an adjuvanted ID93 vaccine towards for future human clinical trials, ultimately resulting in an approved post- exposure TB vaccine.

描述（由申请人提供）：结核病（TB）是结核分枝杆菌（MTB）引起的疾病，是对公共卫生的持续威胁。在全球范围内，大约有20亿人感染了结核病，每年有900万例新诊断的活跃结核病病例造成150万人死亡。此外，对结核病感染的管理不善或不当治疗可能导致耐药性结核病病例的发展，因为治疗既困难又昂贵。 MTB的抗药性菌株无法通过一线治疗治疗并需要12-24个月的复杂第二和第三行抗生素。此外，存在无法用任何可用抗生素治疗的TDR（完全耐药）菌株。当前的建议旨在开发一种新型的协同组合化学免疫治疗方案，用于治疗由MTB引起的感染，包括多种，极高和完全耐药的菌株。一种有效的治疗方法可将细菌负荷降低并缩短治疗少于六个月，将在大大降低这种病原体的影响方面起重要作用。该应用是我们为开发结核病疫苗的系统和有条理的方法的扩展。在过去的二十年中，我们将此策略应用于开发M72/AS01E（目前正在II期临床试验中）和ID93/GLA-SE将其用于可行的疫苗候选物。目前，据我们所知，ID93/GLA-SE是唯一的结核病疫苗候选者，已在多种结核病动物模型中进行了预防和治疗测试。我们的候选疫苗具有三种保护作用：显着降低了肺细菌负荷，在气溶胶挑战后降低了传播的MTB感染，并在暴露后免疫治疗保护。为此申请提供资金将有助于我们继续努力开发辅助的ID93疫苗，以实现未来的人类临床试验，最终导致经批准的暴露后结核病疫苗。