IMMUNIZE W/ LIVE ATTENUATED SIV INDUCES STRONG TYPE 1 T HELPER RESPONSES

使用减毒活 SIV 进行免疫可引起强烈的 1 型 T 辅助反应

• 批准号: 6116553
• 负责人: MC GAUDUIN
• 金额: $ 10.61万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116553
• 关键词: AIDS; Mammalia; communicable diseases; immunology; inflammation; lymphatic system; vaccines; virus

Immunization with live attenuated SIV strains has proved to be one of the most effective strategies to induce protective immunity in the SIV/macaque model To better understand the role that CD4+ T helper responses may play in mediating protection in this model, we characterized SIV-specific proliferative and cytokine responses in macaques immunized with live attenuated SIV strains Macaques chronically infected with the attenuated virus SIVmac239'nef had strong proliferative responses to SIV proteins, with stimulation indices of up to 72 Limiting dilution and ELISPOT analysis revealed SIV-specific T helper precursor frequencies of up to 200 per 106 PBMC The magnitude of the proliferative response to SIV gag varied inversely with the degree of attenuation gag-specific, but not envelope-specific, responses were lower in animals infected with the more highly attenuated SIV strains SIVmac239'3 and SIVmac239'4 SIV-specific stimulation of lymphocytes from SIVmac 239 'nef-vaccinated macaques resulted in secretion of interferon-gamma, RANTES, MIP-1alpha and MIP-1beta but not IL-4 or IL-10 Intracellular flow cytometric analysis confirmed the production of IL-2, IFN-gamma, RANTES and MIP-1beta by CD4+ T cells following p55 stimulation The ability of live attenuated SIV to induce a strong, sustained type 1 T helper response may play a role in the success of this vaccination approach to generate protection against challenge with wild-type SIV Aldovini, A - Children's Hospital, Harvard Medical School Analysis of immune responses generated by DNA vaccination Bunnel, B - Ohio State University In vivo retroviral transduction of hematopoietic stem cells Crooks, G - Children's Hospital of Los Angeles In vitro T lymphopoiesis of single hematopoietic cells using rhesus thymic stromal cultures Dube', I - University of Toronto Retroviral transduction of rhesus hematopoietic stem cells using long term bone marrow cultures Feinberg, M - Office of AIDS Research, National Institutes of Health, Bethesda, MD Characterization of cell mediated immune responses in SIV infected sooty mangabeys Grant, R - University of California, San Francisco Characterization of cell mediated immune responses in SIV infected sooty mangabeys Hirsch, MS - Massachusetts General Hospital/Harvard Medical School, Boston, MA Interactions between SIV and rhesus cytomegalovirus Jordan, C - University of Kentucky Analysis of foreign gene expression in hematopoietic cells following retroviral transduction of hematopoietic stem cells Knipe, D - Harvard Medical School, Boston, MA Herpesvirus vectors as vaccines for AIDS Letvin, NL - Beth Israel Hospital/Harvard Medical School, Boston, MA Immunophenotyping of rhesus macaques Lisziewicz, J - Research Institute for Genetic and Human Therapy Gene therapy using a polymeric TAR decoy MacVitte, T - University of Maryland Analysis of foreign gene expression in hematopoietic cells following retroviral transduction of hematopoietic stem cells Malech, H - NIH, Bethesda, MD Analysis of foreign gene expression in hematopoietic cells following retroviral transduction of hematopoietic stem cells Marasco, W - Dana Farber Cancer Institute, Boston, MA Human antitat intrabody gene therapy against SHIV McClure, H - Yerkes Regional Primate Research Center/Emery University, Atlanta, GA Characterization of cell mediated immune responses in SIV-infected sooty mangabeys Morgan, R - NIH, Bethesda, MD In vivo transduction of hematopoietic stem cells Mulligan, R - Harvard Medical School, Boston, MA Identification of hematopoietic stem cells Robinson, H - University of Massachusetts Medical School, Worcester, MA Characterization of cytotoxic T lymphocyte responses induced by DNA vaccination Sachs, D - Massachusetts General Hospital/Harvard Medical School, Boston, MA Xenogeneic stem cell and thymic replacement in AIDS Scadden, D - Massachusetts General Hospital/Harvard Medical School, Boston, MA Characterization of hematopoietic stem cells in monkeys and humans Sklar, J - Brigham and Women's Hospital/Harvard Medical School, Boston, MA Analysis of the role of notch and jagged in T cell development Strayer, D - Jefferson Medical College, Philadelphia, PA Transduction of hematopoietic stem cells using SV40-based vectors Sykes, M - Massachusetts General Hospital/Harvard Medical School, Boston, MA Xenogeneic stem cell and thymic replacement in AIDS Walker, BD - Massachusetts General Hospital/Harvard Medical School, Boston, MA Immune reconstitution of HIV-infected individuals Wang, F - Brigham and Women's Hospital/Harvard Medical School, Boston, MA Infection of rhesus macaques with Epstein Barr virus Wong-Staal, F - University of California, San Diego Gene Therapy using a SIV-specific Ribozyme Zimmerberg, J - National Institutes of Health, Bethesda, MD Three dimensional analysis of thymic stromal cultures

用减毒的SIV活毒株进行免疫已被证明是一种 最有效的策略，以诱导保护性免疫， SIV/猕猴模型为了更好地理解CD 4 + T辅助细胞在SIV/猕猴模型中的作用， 反应可能发挥调解保护在这个模型中，我们 特征性SIV特异性增殖和细胞因子反应， 用减毒SIV活毒株免疫的猕猴 慢性感染减毒病毒SIVmac 239 'nef， 对SIV蛋白的强增殖反应， 指数高达72极限稀释和ELISPOT分析显示 SIV特异性T辅助细胞前体频率高达200/106 PBMC 对SIV gag的增殖反应的程度不同， 与特定gag的衰减程度成反比，但不 在感染病毒的动物中， 更高度减毒的SIV毒株SIVmac 239 '3和SIVmac 239' 4 来自SIVmac 239的淋巴细胞的SIV特异性刺激 NEF接种的猕猴导致干扰素-γ的分泌， RANTES、MIP-1 α和MIP-1 β，但不含IL-4或IL-10细胞内 流式细胞术分析证实了IL-2，IFN-γ， p55刺激后CD 4 + T细胞的RANTES和MIP-1 β 减毒活SIV诱导强的、持续的1型T的能力 辅助反应可能在这种疫苗接种的成功中发挥作用 产生针对野生型SIV攻击的保护的方法 Aldovini，A -儿童医院，哈佛医学院分析 由DNA疫苗接种产生的免疫反应Bunnel，B -俄亥俄州 造血干细胞的体内逆转录病毒转导 克鲁克斯，G -洛杉矶儿童医院体外T 恒河猴胸腺单个造血细胞的淋巴细胞生成 基质培养Dube '，I -多伦多大学逆转录病毒 使用长期骨转导恒河猴造血干细胞 Feinberg，M -国家艾滋病研究办公室 健康研究所，Bethesda，MD细胞介导的 SIV感染白眉猴的免疫应答 of加州，旧金山弗朗西斯科 SIV感染的白眉猴的反应，MS -马萨诸塞州 综合医院/哈佛医学院，马萨诸塞州波士顿 SIV和恒河猴巨细胞病毒之间的关系 造血细胞外源基因表达的肯塔基州分析 逆转录病毒转导造血干细胞后， - 哈佛医学院，马萨诸塞州波士顿疱疹病毒载体作为疫苗 Letvin，NL - Beth Israel Hospital/哈佛医学院， Boston，MA恒河猴的免疫表型Lisziewicz，J - 基因和人类治疗研究所使用基因疗法 聚合物TAR诱饵MacVitte，T -马里兰州大学分析 逆转录病毒感染造血细胞后外源基因的表达 造血干细胞的转导Malech，H-NIH，Bethesda，MD 外源基因在造血细胞中的表达分析 造血干细胞逆转录病毒转导 Farber Cancer Institute，Boston，MA人抗tat胞内抗体基因 针对SHIV的治疗麦克卢尔，H -耶基斯地区灵长类动物研究 Center/Emery University，Atlanta，GA细胞介导的 SIV感染的白眉猴的免疫应答，R-NIH， Bethesda，MD造血干细胞的体内转导 Mulligan，R -哈佛医学院，马萨诸塞州波士顿 造血干细胞罗宾逊，H -马萨诸塞州大学 马萨诸塞州伍斯特医学院细胞毒性T细胞的表征 DNA疫苗接种诱导的淋巴细胞反应Sachs，D - 马萨诸塞州总医院/哈佛医学院，马萨诸塞州波士顿 艾滋病中的异种干细胞和胸腺替代 马萨诸塞州总医院/哈佛医学院，马萨诸塞州波士顿 猴和人造血干细胞的特性 Sklar，J -布里格姆妇女医院/哈佛医学院， Boston，MA分析Notch和Jagged在T细胞中的作用 发展斯特雷耶，D -杰斐逊医学院，费城，宾夕法尼亚州 使用基于SV 40的载体转导造血干细胞 M -马萨诸塞州总医院/哈佛医学院， 波士顿，马萨诸塞州艾滋病患者的异种干细胞和胸腺替代步行者， BD -马萨诸塞州总医院/哈佛医学院，马萨诸塞州波士顿 HIV感染者的免疫重建 和妇女医院/哈佛医学院，马萨诸塞州波士顿 恒河猴与爱泼斯坦巴尔病毒Wong-Staal，F -大学 加州，圣地亚哥使用SIV特异性核酶的基因治疗 Zimmerberg，J -国立卫生研究院，Bethesda，MD 3 胸腺基质培养物的量纲分析