Multivalent DNA vaccine-mediated protection against Tuberculosis

多价 DNA 疫苗介导的结核病保护

• 批准号: 10297846
• 负责人: DAVID B. WEINER
• 金额: $ 86.53万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-11-23 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10297846
• 关键词: Address; Adjuvant; Adolescent; Adult; Animals; Antibodies; Antigens; BCG Live; BCG Vaccine; Bacille Calmette-Guerin vaccination; CD8-Positive T-Lymphocytes; Cell physiology; Child; Clinic; Clinical; Clinical Trials; Collection; DNA; DNA Vaccines; Data; Development; Electroporation; Ensure; Epidemic; Flow Cytometry; Formulation; Generations; Genes; Genetic; Goals; Human; Human papillomavirus 16; Immune response; Immunity; Infant; Interleukin-12; Interleukin-15; Lung; Measures; Mediating; Modality; Modeling; Mus; Mycobacterium tuberculosis; Mycobacterium tuberculosis antigens; Outcome; Pathology; Phase; Plasmids; Prevention; Proteins; Pulmonary Tuberculosis; RNA; Sampling; Scheme; Spleen; Stains; Standardization; T cell response; T-Lymphocyte; TNFSF5 gene; Technology; Testing; Time; Tuberculosis; Tuberculosis Vaccines; Vaccinated; Vaccination; Vaccines; Viral Vector; base; candidate selection; cell mediated immune response; cytokine; design; experience; immunogenicity; improved; in vivo; innovation; interleukin-23; lead candidate; mouse model; nonhuman primate; novel; plasmid DNA; prevent; programs; response; success; synthetic construct; therapeutic HPV vaccine; vaccination strategy; vaccine access; vaccine candidate; vaccine delivery; vaccine development; vaccine efficacy; vaccine immunogenicity; vaccine platform; vaccine response; vaccine trial; vector; vector vaccine

An effective TB vaccine remains an elusive goal. The success of BCG in preventing disseminated TB suggests that it is possible to provide complete protection from pulmonary TB or TB infection through an immunization strategy. However, the vaccine-­induced responses elicited by the most recent MVA85A phase II vaccine trial were modest and of limited durability compared to BCG. The immune responses induced in a preferred vaccine should also be superior to those observed using BCG alone. Currently, there is no such TB vaccine available, and few groups have the combination of technologies now proven in the clinic to produce such a platform. This innovative program makes major advances in new DNA adaptive EP + gene adjvuant vaccine technology which in the clinic generates T cell immunity equivalent or superior to live viral vector vaccines. We will build on our recent clinical success by newer genetic adjuvants focused on improved T-­cell and antibody induction. We concentrate on increasing the breadth of coverage induced by these designed DNA vaccine by exploring the potential of a multivalent DNA vaccine targeting multiple Mtb antigens at both active and latent stages of TB infection. Furthermore, we plan to develop this collection of technologies in a simplified vaccine scheme that has distinct clinical advantages for global testing. There are three aims that comprise this program to address these issues.

有效的结核病疫苗仍然是一个难以捉摸的目标。 BCG在预防传播结核病方面的成功表明 可以通过免疫提供完全保护肺结核或结核病感染的完全保护 战略。但是，疫苗诱导的反应是由最新的MVA85A II期疫苗试验引起的 与BCG相比，适度且耐用性有限。在首选疫苗中诱导的免疫调查 仅使用BCG观察到的那些也应该优于那些。目前，没有这样的结核病疫苗， 而且很少有小组现在在诊所中证明了这种平台的结合。 创新计划在新的DNA自适应EP +基因相邻疫苗技术方面取得了重大进展 在诊所中，与活病毒载体疫苗相当于T细胞免疫学或优越。我们将在我们的基础上建立 较新的遗传调节器的最新临床成功重点是改善T细胞和抗体诱导。我们 专注于增加这些设计的DNA疫苗引起的覆盖范围的广度 靶向多种MTB抗原在TB的活性和潜在阶段的多价DNA疫苗的潜力 感染。此外，我们计划在具有简化的疫苗方案中开发此技术集合 全球测试的独特临床优势。有三个目的完成此程序来解决这些问题 问题。