Optimization of a Multivalent Tuberculosis Vaccine

多价结核疫苗的优化

• 批准号: 7326572
• 负责人: Anne Searls DeGroot
• 金额: $ 29.99万
• 依托单位: EPIVAX, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7326572
• 关键词: Address; Adjuvant; Aerosols; Algorithms; Alleles; Antigen Targeting; Antigens; Award; Bacillus (bacterium); Biological Markers; Cells; Cellular Immunity; Class; Collaborations; Computer software; Condition; Consult; DNA; DNA Vaccines; Development; Disease; Dose; Electroporation; Enzyme-Linked Immunosorbent Assay; Enzymes; Epitopes; Flow Cytometry; Foundations; Funding; Genome; Goals; Histopathology; Immune; Immune response; Immunity; Immunization; Immunologist; Immunophenotyping; Immunosorbents; Individual; Infection; Interferon Type II; Intramuscular; Leukocytes; Link; Lung; Maps; Massachusetts; Measures; Mediating; Medical center; Modeling; Mus; Mycobacterium tuberculosis; Needlestick Injuries; Oligonucleotides; Peptides; Performance; Phase; Phase II Clinical Trials; Predisposition; Production; Proteins; Protocols documentation; Recombinants; Relative (related person); Research; Research Activity; Research Personnel; Route; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Spleen; Splenocyte; Staging; Standards of Weights and Measures; T-Lymphocyte; T-Lymphocyte Epitopes; Testing; TimeLine; Transgenic Mice; Treatment Protocols; Tuberculosis; Tuberculosis Vaccines; United States National Institutes of Health; Universities; Vaccinated; Vaccination; Vaccine Research; Vaccines; Work; base; cytokine; experience; immunogenicity; improved; in vivo; in vivo Model; innovation; novel; prevent; programs; research study; subcutaneous; tool; vaccination strategy; vaccine efficacy; vaccine evaluation

DESCRIPTION (provided by applicant): This new Phase I SBIR proposal addresses the continuing worldwide need for a tuberculosis (TB) vaccine. We detail a novel multivalent strategy that aims to elicit immunity to prevent reactivation of latent TB. This epitope-driven, DNA-prime, protein-boost TB vaccine has been in development since 1997, when our immunoinformatics tools were first applied to identify T cell epitopes from TB proteins. In progress made during the three years of NIH and Sequella/Aeras TB Foundation support, we completed mapping of three sets of TB epitopes including novel epitopes predicted directly from the TB CDC1551 genome. In the next phase of the research program, building on our own experiences and our collaborations, we seek to develop the optimal vaccination strategy, using HLA transgenic mice as the model for in vivo study. Before the start of the performance period, we will make the final epitope selections. In the course of the SBIR award period, selected epitopes will be formulated as DNA and peptide/protein vaccines. By means of a prime-boost vaccination strategy, we will optimize key vaccination parameters (administration route, antigen targeting, adjuvant) to induce the greatest immunogenicity as assessed by cytokine production of stimulated immune cells. Next, we will determine the protective efficacy of the optimized TB vaccine against the standard bacilli Calmette-Gu¿rin (BCG) vaccine and as a boost in HLA transgenic mice pre-vaccinated with BCG. Successful completion of this work will set the stage for Phase II development that will partner the vaccine with improved recombinant BCG vaccines and assess efficacy in additional strains of HLA transgenic mice.

描述（由申请人提供）：这项新的 I 期 SBIR 提案解决了全球对结核病 (TB) 疫苗的持续需求，我们详细介绍了一种新颖的多价策略，旨在引发免疫以防止潜伏结核病的重新激活。自 1997 年以来，我们的免疫信息学工具首次用于识别结核蛋白中的 T 细胞表位，因此一直在开发初级蛋白质增强结核病疫苗。在 NIH 和 Sequella/Aeras 结核病基金会的三年支持下，我们根据自己的经验和合作完成了三组结核病表位的绘制，其中包括直接从结核病 CDC1551 基因组预测的新表位。我们寻求开发最佳的疫苗接种策略，使用 HLA 转基因小鼠作为体内研究的模型，在表现期开始之前，我们将在 SBIR 奖项的过程中进行最终的表位选择。在此期间，选定的表位将被配制为DNA和肽/蛋白质疫苗，通过初免-加强疫苗接种策略，我们将优化关键疫苗接种参数（给药途径、抗原靶向、佐剂），以诱导通过细胞因子产生评估的最大免疫原性。接下来，我们将确定优化的结核疫苗对标准杆菌 Calmette-Gu 的保护功效。这项工作的成功完成将为 II 期开发奠定基础，该疫苗将与改进的重组 BCG 疫苗配合使用，并评估其他 HLA 菌株的功效。转基因小鼠。