GENE EXPRESSION PROFILING OF AIDS VACCINE STRATEGIES

艾滋病疫苗策略的基因表达谱分析

• 批准号: 7268028
• 负责人: MICHAEL G KATZE
• 金额: $ 24.18万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7268028
• 关键词: AIDS Vaccines; Acquired Immunodeficiency Syndrome; Acute; Adenoviruses; Animal Experimentation; Animals; Antibodies; Antigens; Bioinformatics; Biology; Blood; Blood specimen; Collaborations; Control Animal; Control Groups; Cytotoxic T-Lymphocytes; DNA Microarray Chip; DNA Microarray format; Data; Data Set; Depth; Development; Disease; Disease Progression; Ebola virus; Evolution; Gene Expression; Gene Expression Profiling; Genes; Genome; Genomics; Grant; HIV; HIV Infections; Hepatitis C; Herpes Simplex Infections; Immune; Immune response; Immunity; Immunization; Infection; Influenza; Informatics; Laboratories; Longitudinal Studies; Macaca; Macaca mulatta; Modeling; Molecular Profiling; National Cancer Institute; Oligonucleotide Microarrays; Pathogenesis; Pathway interactions; Pattern; Phase; Predisposition; Process; Proteins; Protocols documentation; Publishing; Qualifying; Range; Reagent; Recombinant Vaccines; Recombinants; Research; Research Infrastructure; Resources; SARS coronavirus; SIV; Safety; Sampling; Staging; System; Techniques; Technology; Time; Treatment Protocols; Vaccination; Vaccine Research; Vaccines; Vaccinia; Viral; Viral Load result; Viral Pathogenesis; Viral Proteins; Viremia; Week; Work; acquired immunity; attenuation; base; functional genomics; immunogenicity; in vivo; innovation; insight; member; nonhuman primate; novel vaccines; pathogen; programs; research clinical testing; research study; response; simian human immunodeficiency virus; tool; vaccine evaluation; virus host interaction

DESCRIPTION (provided by applicant): In response to the Innovation Grant Program for AIDS Vaccine Research (PA-03-082), we propose to use a functional genomics approach to identify biologically relevant changes in cellular gene expression in response to alternative AIDS vaccine strategies. These analyses will be performed using blood samples obtained from rhesus macaques (Macaca mulatta) in an ongoing vaccine study being conducted by Dr. Marjorie Robert-Guroff at the Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute. This vaccine study is using macaques to evaluate the contribution of HIV envelope subunit boosts to the immunogenicity of a replicating adenovirus (Ad)-HIV/SIV recombinant vaccine. Our collaboration with Dr. Robert-Guroff has the important advantage of expanding the types of data collected for this study without the need for additional animal experimentation. With the recent sequencing of the rhesus macaque genome, and our development of macaque-specific genomic reagents, we have for the first time at our disposal the species-specific tools needed to successfully carry out these studies. We will use the newly developed macaque genomic resources to perform global gene expression analyses on blood samples obtained from animals prior to immunization, at week 14 (after the second immunization with the Ad-HIV/SIV recombinants), immediately prior to challenge at week 44 (after protein boosting of Groups 2 and 3), and at time points corresponding to acute-phase and set-point viral burdens. A total of five time points will be analyzed, with samples obtained from all 6 animals from each immunization or control group, resulting in 120 samples. For the vaccine test groups, expression profiles will be analyzed for patterns that correlate with acquired immunity (e.g., specific cytotoxic T-lymphocytes or antibodies), as well as for expression differences that are associated with the attenuation of disease. Longitudinal studies over vaccination stages will show the temporal evolution of features associated with each immunization strategy and may furnish mechanistic insights into the process. Analysis of the infected, non-immunized control animals will furnish a detailed view of those genes and pathways altered in the course of disease progression, consequently giving a more comprehensive view of viral pathogenesis in these models. It is our hypothesis that genomic profiling of the blood will reveal gene expression changes that are indicative of the host response to vaccination. These profiles may reveal genomic markers of protective immunity or gene expression changes that are indicative of a predisposition to a particular response to immunization and subsequent challenge. Ultimately, these studies may also suggest mechanisms to enhance current AIDS vaccine strategies.

描述（由申请人提供）：响应艾滋病疫苗研究的创新赠款计划（PA-03-082），我们建议使用功能基因组学方法来鉴定细胞基因表达的生物学相关变化，以响应替代性艾滋病疫苗策略。这些分析将使用从恒河猴（Macaca Mulatta）获得的血液样本进行，该研究由Marjorie Robert-Guroff博士在正在进行的疫苗研究中，该研究在国家癌症研究所疫苗疫苗分支机构的逆转录病毒感染免疫生物学部分。这项疫苗研究使用猕猴评估HIV包膜亚基对复制腺病毒（AD）-HIV/SIV/SIV重组疫苗的免疫原性的贡献。我们与罗伯特·古罗夫（Robert-Guroff）博士的合作具有扩大本研究收集数据类型的重要优势，而无需进行其他动物实验。随着恒河猴猕猴基因组的最新测序，以及我们对猕猴特异性基因组试剂的发展，我们首次可以使用成功进行这些研究所需的物种特定的工具。我们将使用新开发的猕猴基因组资源来对在免疫之前从动物获得的血液样本进行全球基因表达分析，即在第14周（在第二次使用AD-HIV/SIV重组分子进行第二次免疫后），直到第44周进行挑战之前（第2和3组的蛋白质增强后），以及与蛋白质的提升后，以及与Aucute-Phase-phase-phase-phase-phase-phase-phase-phase and set bur bur burd burd burd burd。将分析总共五个时间点，并从每个免疫或对照组的所有6只动物中获得样品，从而产生120个样本。对于疫苗测试组，将分析与获得的免疫力相关的模式（例如，特定的细胞毒性T-淋巴细胞或抗体），以及与疾病衰减相关的表达差异。关于疫苗接种阶段的纵向研究将显示与每种免疫策略相关的特征的时间演变，并可能对该过程提供机械洞察力。对感染的，非免疫对照动物的分析将提供对疾病进展过程中改变的基因和途径的详细视图，从而在这些模型中更全面地看待病毒发病机理。我们的假设是，血液的基因组分析将揭示基因表达变化，这表明宿主对疫苗接种的反应。这些特征可能揭示了保护性免疫或基因表达变化的基因组标记，这表明对免疫的特定反应和随后的挑战具有倾向。最终，这些研究还可能提出增强当前艾滋病疫苗策略的机制。