Consensus Gene-Based Immunogens in Rhesus Monkeys

HIV-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。最近在老鼠身上的研究表明，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创造有效疫苗的影响。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大的模型。我们将使用这个动物模型来探索使用“集中式”基于基因的HIV-1疫苗策略来扩大疫苗引发的免疫反应的识别特异性。具体地说，我们将使用此模型来探索： 1.选择最佳的“集中式”HIV-1包膜免疫原。 2.集中免疫原与当代HIV-1Gag-polnef免疫原的比较。 3.“集中式”和“多分支”HIV-1免疫原的比较 4.重组MVA“集中式”HIV-1免疫原的评估。 5.对“集中式”包膜亚单位免疫原的评价。

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.