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实现的目标。卡介苗在预防播散性结核病方面的成功表明 通过免疫接种可以完全预防肺结核或肺结核的感染 策略。然而，最近的MVA85A第二阶段疫苗试验引发了疫苗诱导的反应 与卡介苗相比，卡介苗的耐受性有限。首选疫苗诱导的免疫反应 也应该比单独使用卡介苗观察到的效果更好。目前，还没有这样的结核病疫苗， 而且，很少有集团拥有目前在临床上得到验证的技术组合来生产这样一个平台。这 创新计划在新的DNA适应性EP+基因佐剂疫苗技术方面取得重大进展 在临床上产生等同于或优于活病毒载体疫苗的T细胞免疫。我们将在我们的 最近，新型基因佐剂在临床上的成功主要集中在改善T细胞和抗体诱导方面。我们 集中精力通过探索这些设计的DNA疫苗的覆盖范围来增加覆盖范围 针对结核病活动期和潜伏期多个结核分枝杆菌抗原的多价DNA疫苗的可能性 感染。此外，我们计划在简化的疫苗计划中开发这一技术集合，该计划具有 全球测试具有明显的临床优势。这项计划有三个目标来解决这些问题 问题。