Consensus Gene-Based Immunogens in Rhesus Monkeys

恒河猴中基于共识基因的免疫原

• 批准号: 7756632
• 负责人: SAMPA SANTRA
• 金额: $ 37.34万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7756632
• 关键词: AIDS Vaccines; Administrator; Advisory Committees; Animal Model; Antigens; Communication; Consensus; Development; Ensure; Evaluation; Gagging; Genes; Genetic Variation; Grant; HIV vaccine; HIV-1; HIV-1 vaccine; Immune response; Macaca mulatta; Manuscripts; Modeling; Mus; National Institute of Allergy and Infectious Disease; Occupational activity of managing finances; Operative Surgical Procedures; Peptides; Preparation; Principal Investigator; Process; Production; Recombinants; Reporting; Research; SIV; Site; Specificity; TimeLine; Travel; Vaccines; base; gene synthesis; meetings; programs; simian human immunodeficiency virus; symposium; transmission process; working group

The extreme genetic diversity of HIV-1 isolates poses a major challenge for the development of an HIV vaccine. Recent studies in mice have suggested that using "centralized" HIV-1 sequences in immunogens may be an effective strategy for minimizing the impact of this genetic diversity on the creation of effective vaccines. Simian immunodeficiency virus (SIV) and the simian human immunodeficiency virus (SHIV) infected rhesus monkeys provide a powerful model for evaluating potential HIV vaccine strategies. We will employ this animal model to explore the use of "centralized" gene-based HIV-1 vaccine strategies for broadening the recognition specificity of vaccine-elicited immune responses. Specifically, we will use this model to explore the: 1. Selection of an optimal "centralized" HIV-1 envelope immunogen. 2. Comparison of "centralized" and contemporary HIV-1 gag-pol-nef immunogens. 3. Comparison of "centralized" and multiclade HIV-1 immunogens 4. Assessment of recombinant MVA "centralized" HIV-1 immunogens. 5. Evaluation of "centralized" envelope subunit immunogens.

艾滋病毒-1分离株的极端遗传多样性对艾滋病毒疫苗的开发构成了重大挑战。最近对小鼠的研究表明，在免疫原中使用“集中的”HIV-1序列可能是一种有效的策略，可以最大限度地减少这种遗传多样性对制造有效疫苗的影响。猴免疫缺陷病毒（SIV）和猴人类免疫缺陷病毒（SHIV）感染的恒河猴为评估潜在的HIV疫苗策略提供了一个强有力的模型。我们将采用这种动物模型来探索“集中式”基于基因的HIV-1疫苗策略的使用，以扩大疫苗引发的免疫反应的识别特异性。具体来说，我们将使用这个模型来探索：