GENETICALLY DEFINED HERPES/RETROVIRUS SPF MACAQUES: AIDS: VACCINE DVMT

基因定义的疱疹/逆转录病毒 SPF 猕猴：艾滋病：疫苗 DVMT

• 批准号: 8359522
• 负责人: NICHOLAS WILLIAM LERCHE
• 金额: $ 25.13万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8359522
• 关键词: AIDS Vaccines; Acquired Immunodeficiency Syndrome; Address; Alleles; Animals; Antibodies; Biological Assay; Breeding; Chinese People; Complex; Cytomegalovirus; Data; Detection; Development; Frequencies; Funding; Genotype; Goals; Haplotypes; Herpesviridae; Immune response; In Vitro; MHC Class II Genes; Macaca; Macaca mulatta; Methods; Microsatellite Repeats; Natural History; Polymerase Chain Reaction; Production; Research; Research Personnel; Retroviridae; Rhadinovirus; SIV; Screening procedure; Simian Foamy Virus; Simian T-lymphotropic virus 1; Specific Pathogen Frees; System; Type D Retrovirus; United States National Institutes of Health; Viral; Viral Antigens; Virus; Virus Shedding; cell mediated immune response; cost; cost effectiveness; genetic pedigree; genetic profiling; germ free condition; high throughput screening; meetings; offspring; pathogen; programs; response; sound

DESCRIPTION (Provided by applicant): The goal of this project is to expand the production of genetically characterized rhesus macaques that are specific pathogen free (SPF) for an extended list of persistent viruses, including simian immunodeficiency virus (SIV), simian T-lymphotropic virus (STLV-1), simian type D retrovirus (SRV-D), simian foamy virus (SFV), Cercopithecine herpesvirus I (B virus), rhesus cytomegalovirus (RhCMV), and rhesus rhadinovirus (RRV). This expansion will be geared to the production of SPF animals for use in AIDS-related and other NIH-funded research, and to establishing a long-term SPF breeding colony of rhesus macaques with known pedigrees and well-defined major histocompatability complex (MHC) genotypes. To meet these objectives, the investigators will derive SPF offspring from conventional non-SPF rhesus breeding stock of Chinese origin. An expanded program of MHC typing will be used to characterize breeding stock and offspring that will include additional microsatellite loci, class I alleles and class II genes. This expanded MHC typing will facilitate the identification and definition of immune response genotypes, and will allow for selected breeding to produce animals with specific genetic profiles in response to shifting research needs. Data generated by these studies will also allow the investigators to determine whether significant differences in MHC haplotype frequencies (which could reflect differences in immune response) exist between Chinese origin and Indian origin rhesus macaques. The determination and confirmation of B virus status has proven to be one of the most problematic aspects of SPF colony development. Augmented B virus screening utilizing polymerase chain reaction detection of viral shedding and in vitro assessment of cell-mediated immune responses to B virus antigens will be implemented for B virus surveillance. These studies will provide information on aspects of the natural history of B virus critical to the sound management and continued integrity of SPF macaque colonies. As the number of animals involved in SPF programs increases and the list of specific pathogens expands, there is a need for increased efficiency and cost-effectiveness of methods used for large-scale screening. To address this need, the investigators will optimize and validate a multiplex system for sero-detection of antibodies to multiple viral agents in a single assay. This multiplex system will allow for high throughput screening at reduced cost and will be used in support of the SPF colony development.

描述(由申请人提供)：这个项目的目标是扩大恒河猴的生产，这些恒河猴对一系列持久病毒，包括猴免疫缺陷病毒(SIV)、猴T淋巴细胞嗜淋巴病毒(STLV-1)、猿D型逆转录病毒(SRV-D)、猴泡沫病毒(SFV)、脑炎疱疹病毒I(B病毒)、恒河猴巨细胞病毒(RhCMV)和恒河猴横纹病毒(RRV)都没有特殊病原体(SPF)。这一扩展将用于生产SPF动物，用于艾滋病相关研究和其他NIH资助的研究，并建立一个长期的SPF猕猴繁殖群体，这些猕猴具有已知的系谱和明确的主要组织相容性复合体(MHC)基因类型。为了达到这些目标，研究人员将从中国起源的传统非SPF猕猴种群中获得SPF后代。一个扩展的MHC分型程序将用于鉴定种畜和后代的特征，其中将包括额外的微卫星座位、I类等位基因和II类基因。这种扩大的MHC分型将有助于免疫反应基因类型的识别和定义，并将允许精选育种生产具有特定基因图谱的动物，以响应不断变化的研究需求。这些研究产生的数据还将使研究人员确定中国猕猴和印度猕猴在MHC单倍型频率(可能反映免疫反应的差异)方面是否存在显著差异。B病毒状态的确定和确认已被证明是SPF菌落发展最有问题的方面之一。将利用聚合酶链式反应检测病毒脱落和体外评估细胞介导的对B病毒抗原的免疫反应来加强B病毒筛查，以监测B病毒。这些研究将提供有关B病毒自然历史方面的信息，这些信息对SPF猕猴群体的健全管理和持续完整性至关重要。随着SPF项目涉及的动物数量的增加和特定病原体清单的扩大，需要提高用于大规模筛查的方法的效率和成本效益。为了满足这一需求，研究人员将优化和验证一种多重系统，用于在一次检测中对多种病毒剂的抗体进行血清检测。这种多路系统将允许以较低的成本进行高通量筛选，并将用于支持SPF菌落的发展。