Antigenicity and Immunogenicity of Stabilized prefusion F protein

稳定预融合 F 蛋白的抗原性和免疫原性

• 批准号: 9551287
• 负责人: Barney Graham
• 金额: $ 111.33万
• 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/9551287
• 关键词: Adult; Antigens; Biological Assay; CD8-Positive T-Lymphocytes; Chemistry; Disease; Epitopes; Glycoproteins; Goals; Immune response; Immunization; Intervention; Maps; Modeling; Molecular Conformation; Mus; Nucleic Acids; Phase I Clinical Trials; Post-Translational Protein Processing; Proteins; Research; Respiratory Syncytial Virus Vaccines; Safety; Serological; Site; Structure; Surface; Vaccine Antigen; Vaccines; aluminum sulfate; base; design; immunogenicity; improved; neutralizing antibody; novel; research clinical testing; response; vaccine development; vector

Immunogens inducing protective, disease-sparing CD8+ T cell responses are a primary focus of research efforts at the VRC. These studies are designed to identify interventions that will increase the efficiency of nucleic acid and vector-based immunization and to optimize the conditions of each intervention. The magnitude and the quality of the immune responses induced by each vector will be compared using murine prime-challenge models. The RSV F glycoprotein is a key target for vaccine-induced neutralizing antibody. Our hypothesis is that understanding the mechanism of antibody neutralization will be facilitated by defining the structure of F and the structure of epitopes associated with neutralization. This will allow novel antigen design. Characterizing the chemistry and post-translational modifications in F will also promote improved vaccine antigen design. We have advanced our stabilized prefusion F protein into clinical evaluation in a Phase 1 clinical trial, VRC 317. In this trial, we are evaluating safety, tolerability, and immunogenicity of our stabilized prefusion F protein (DS-Cav1) with or with alum adjuvant in healthy adults.

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。这些研究旨在确定将提高核酸和基于媒介的免疫效率并优化每种干预措施的干预措施。 每种载体引起的免疫反应的大小和质量将使用鼠主要挑战模型进行比较。 RSV F糖蛋白是疫苗诱导的中和抗体的关键靶标。我们的假设是，通过定义F结构和与中和相关的表位结构来了解抗体中和的机理。这将允许新颖的抗原设计。表征F中的化学和翻译后修饰也将促进改进的疫苗抗原设计。 在1期临床试验中，我们已经将稳定的预融合F蛋白提高到临床评估，即VRC 317。在这项试验中，我们正在评估健康成年人中稳定的预灌注F蛋白（DS-CAV1）的安全性，耐受性和免疫原性。