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.

免疫原诱导保护性的、疾病免疫的CD8+T细胞反应是VRC研究工作的主要重点。DNA疫苗是目前候选疫苗的主要平台。虽然DNA免疫原可以产生CD8+CTL反应，但需要大量注射DNA才能诱导免疫。这些研究旨在确定将提高DNA免疫效率的干预措施，并优化每种干预措施的条件。随着增加疫苗DNA摄取和/或表达的程序的确定，将需要更少的DNA管理，使DNA疫苗的使用更广泛地适用，特别是在发展中国家。此外，还将评估表达匹配的密码子修饰病毒蛋白的载体免疫原诱导病毒特异性免疫反应的相对能力。具体地说，每个载体诱导的免疫反应的大小和质量将使用小鼠主要挑战模型进行比较。