Multivalent DNA vaccine-mediated protection against Tuberculosis

多价 DNA 疫苗介导的结核病保护

• 批准号: 10054982
• 负责人: DAVID B. WEINER
• 金额: $ 90.84万
• 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 2022-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10054982
• 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; Immunization; Infant; Interleukin-12; Interleukin-15; Lung; Measures; Mediating; Modality; Modeling; Mus; Mycobacterium tuberculosis; 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; vaccine access; vaccine candidate; vaccine delivery; vaccine development; vaccine efficacy; 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 有可能通过免疫接种提供对肺结核或结核感染的完全保护 战略然而，最近的MVA85A II期疫苗试验引起的疫苗接种诱导的应答， 与BCG相比，其适度和有限的耐久性。在优选的疫苗中诱导的免疫应答 也应该上级单独使用BCG观察到的那些。目前，还没有这种结核病疫苗， 并且很少有小组具有现在在临床上被证明的技术组合来产生这样的平台。这 创新计划在新DNA适应性EP +基因佐剂疫苗技术方面取得了重大进展， 在临床上产生相当于或上级于活病毒载体疫苗的T细胞免疫。我们将建立在我们的 最近的临床成功的新的遗传佐剂集中在改善T细胞和抗体诱导。我们 集中精力增加这些设计的DNA疫苗诱导的覆盖范围， 在结核病活动期和潜伏期靶向多种Mtb抗原的多价DNA疫苗的潜力 感染此外，我们计划在一个简化的疫苗方案中开发这一系列技术， 全球测试的独特临床优势。有三个目标，包括该计划，以解决这些问题 问题.