HIV 1 VACCINE AND IMMUNITY STUDY

HIV 1 疫苗和免疫研究

• 批准号: 6374065
• 负责人: LUNG-JI CHANG
• 金额: $ 7.23万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6374065
• 关键词: AIDS vaccines; SCID mouse; T lymphocyte; active immunization; antiAIDS agent; antibody formation; biological models; drug screening /evaluation; enzyme linked immunosorbent assay; flow cytometry; human immunodeficiency virus 1; leukocyte activation /transformation; model design /development; vaccine development

Understanding the mechanisms of pathogenesis and host immunity is critical to the success of developing an effective HIV vaccine. Studies of non-HIV lentiviruses in animals have identified viral pathogenesis factors and host humoral and/or cellular effectors essential to a protective immunity. The protective immunity seen in animals, however, does not always correlate with that in a human infection. An in vivo model for direct evaluation of HIV immunity is urgently needed. In this pilot project, we propose to further explore the human peripheral blood lymphocyte-scid/beige mouse model (hu-PBL-scid/bg) for the evaluation of HIV vaccines and host immunity. Using this model, we have previously shown that multiply exposed, HIV-seronegative individuals have protective immunity could be evoked via vaccination., and the hu-PBL- scid/bg mouse model could be a useful for studies of HIV vaccines and host immunity. Most of the HIV vaccines under clinical trials are based on subunit peptides, recombinant proteins, eukaryotic viral or non-viral vectors. Even through whole viral vaccines have been successfully used for treating various viral diseases, whole-HIV based vaccines have not been tested in humans because of concerns of possible HIV infection. Several HIV-1 vaccine constructs have been generated based on replicative and non-replicative HIV-1 recombinants. In this pilot study, different HIV-1 vaccine constructs will be tested, and the in vivo HI immunity in patients under highly active anti-retroviral therapy (HAART) will also be examined using the scid/beige mouse model. There are two specific aims in this pilot study. 1) To examine primary and secondary immune responses in the hu-PBL- scid/bg mice using antigens including different HIV-1 vaccine constructs; and 2) To assess the immune functions of HAART patients by using the scid/bg in vivo model. Data obtained from this pilot study will be used to support further development of the hu-PBL-scid/bg mouse model.

了解发病机制和宿主免疫对于成功开发有效的艾滋病毒疫苗至关重要。对动物中非 HIV 慢病毒的研究已经确定了病毒发病机制以及对保护性免疫至关重要的宿主体液和/或细胞效应子。然而，动物的保护性免疫并不总是与人类感染的相关。迫切需要一种直接评估艾滋病毒免疫力的体内模型。在这个试点项目中，我们建议进一步探索人外周血淋巴细胞-scid/米色小鼠模型（hu-PBL-scid/bg）用于评估HIV疫苗和宿主免疫。使用该模型，我们之前已经证明，多次暴露的 HIV 血清阴性个体可以通过疫苗接种激发保护性免疫力。并且 hu-PBL-scid/bg 小鼠模型可用于 HIV 疫苗和宿主免疫的研究。大多数临床试验中的HIV疫苗都是基于亚基肽、重组蛋白、真核病毒或非病毒载体。尽管全病毒疫苗已成功用于治疗各种病毒性疾病，但由于担心可能感染艾滋病毒，基于艾滋病毒的全疫苗尚未在人体中进行测试。基于复制型和非复制型 HIV-1 重组体，已经产生了几种 HIV-1 疫苗构建体。在这项试点研究中，将测试不同的 HIV-1 疫苗结构，并使用 scid/beige 小鼠模型检查接受高效抗逆转录病毒治疗 (HAART) 的患者的体内 HI 免疫力。这项试点研究有两个具体目标。 1) 使用包括不同 HIV-1 疫苗构建体的抗原检查 hu-PBL-scid/bg 小鼠的初次和二次免疫反应； 2)利用scid/bg体内模型评估HAART患者的免疫功能。从该试点研究中获得的数据将用于支持 hu-PBL-scid/bg 小鼠模型的进一步开发。