Vectors and Methods to Increase Immunogenicity during DNA Vaccination

DNA 疫苗接种过程中提高免疫原性的载体和方法

• 批准号: 7964850
• 负责人: Barney Graham
• 金额: $ 26.73万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7964850
• 关键词: Antigens; CD8B1 gene; Codon Nucleotides; DNA; DNA Vaccines; Developed Countries; Developing Countries; Disease; Genes; Goals; Immune response; Immunity; Immunization; Intervention; Methodology; Methods; Modeling; Mus; Phenotype; Procedures; Relative (related person); Research; Research Design; System; T-Lymphocyte; Treatment Protocols; Vaccination; Vaccines; Viral Proteins; Virus; base; immunogenicity; plasmid DNA; response; uptake; vaccine candidate; vector

Immunogens inducing protective, disease-sparing CD8+ T cell responses are a primary focus of research efforts at the VRC. DNA vaccines are the chief platform of vaccine candidates currently. While DNA immunogens can generate CD8+ CTL responses, administration of large quantities of DNA is required to induce immunity. These studies are designed to identify interventions that will increase the efficiency of DNA immunization and to optimize the conditions of each intervention. With the identification of procedures that increase the uptake and/or expression of vaccine DNA, the administration of less DNA would be required, making the use of DNA vaccines more widely applicable, particularly in developing countries. Additionally, vector-based immunogens expressing matched codon-modified viral proteins will be evaluated for their relative abilities to induce virus-specific immune responses. Specifically, the magnitude and the quality of the immune responses induced by each vector will be compared using murine prime-challenge models.

诱导保护性，疾病的CD8+ T细胞反应的免疫原子是VRC研究工作的主要重点。 DNA疫苗是目前疫苗候选物的主要平台。虽然DNA免疫原子可以产生CD8+ CTL反应，但需要大量DNA的给药才能诱导免疫。这些研究旨在确定将提高DNA免疫效率并优化每种干预措施的干预措施。 通过鉴定增加疫苗DNA摄取和/或表达的程序，需要使用较少的DNA给药，从而使使用DNA疫苗更广泛地适用，尤其是在发展中国家。 此外，将评估表达匹配密码子修饰的病毒蛋白的基于载体的免疫原，以诱导病毒特异性免疫反应的相对能力评估。 具体而言，将使用鼠素挑战模型比较每个载体引起的免疫反应的大小和质量。