NHP MHC COMPLEX ALLELE DISCOVERY AND TYPING TECHNOLOGY DEVELOPMENT - HIV/AIDS

NHP MHC 复杂等位基因发现和分型技术开发 - HIV/AIDS

• 批准号: 10018596
• 负责人: DANIEL GERAGHTY
• 金额: $ 62.21万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2020-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10018596
• 关键词: AIDS/HIV problem; Alleles; Animal Model; Biological; Complex; Data; Disease; Frequencies; Genetic; Genomics; Genotype; Goals; HIV vaccine; Haplotypes; Health; Health Sciences; Human; IgG Receptors; Immune response; Immunoglobulins; Institutes; Killer Cells; Knowledge; Macaca; Macaca mulatta; Major Histocompatibility Complex; Major Histocompatibility Complex Gene; Methods; Oregon; Phase; Prevention strategy; Program Development; Receptor Gene; Resources; SIV; SIV Vaccines; Study models; Testing; Translations; Universities; Vaccine Therapy; Vaccines; cell mediated immune response; cohort; gene discovery; gene therapy; knowledge base; nonhuman primate; receptor; success; technology development; vaccination strategy; vaccine evaluation; vaccine trial

“The goals of the NHP MHC Gene Discovery and Typing Development Program are to advance the detailed knowledge base of nonhuman primate (NHP) major histocompatibility complex (MHC) genetic loci, alleles, and haplotypes, and their frequencies; expand discovery and characterization of NHP killer-cell immunoglobulin-like receptors (KIRs) genes, alleles, haplotypes, and frequencies; and develop robust, high-throughput genotyping and haplotyping methods.” Currently the Indian rhesus macaque is one of the most widely used models for studying a variety of human health issues, ranging from diseases and disorders to potential therapies and preventive strategies. It is currently the best animal model for HIV vaccine testing, with the recent success of the RhCMV/SIV vaccination strategy contributing a most convincing example. Since cell-mediated immune responses to SIV are apparently crucial for this (and other) vaccine protection, a complete knowledge of the genetics of the immune response in macaques is essential for translation of results from the animal model to humans. This project will establish phased genomic sequences from the MHC class I and II regions and from KIR for rhesus macaques from the macaque SIV vaccine trial cohort tested at the Vaccine and Gene Therapy Institute at the Oregon Health & Sciences University; and establish phased genomic sequences from the Fc gamma receptor (FCGR) gene complex in 3 macaque species.

NHP MHC基因发现和分型开发计划的目标是推进关于非人灵长类(NHP)主要组织相容性复合体(MHC)遗传位点、等位基因和单倍型及其频率的详细知识库；扩大NHP杀伤细胞免疫球蛋白样受体(KIR)基因、等位基因、单倍型和频率的发现和表征；并开发可靠、高通量的基因分型和单倍型分析方法。 目前，印度恒河猴是研究各种人类健康问题的最广泛使用的模型之一，范围从疾病和障碍到潜在的治疗和预防策略。它是目前HIV疫苗测试的最佳动物模型，最近RhCMV/SIV疫苗接种策略的成功提供了一个最令人信服的例子。由于对SIV的细胞介导的免疫反应显然对这种(和其他)疫苗保护至关重要，因此对猕猴免疫反应的遗传学完全了解对于将动物模型的结果转化到人类是至关重要的。该项目将从俄勒冈健康与科学大学疫苗和基因治疗研究所测试的猕猴SIV疫苗试验队列中建立恒河猴MHC I类和II类区域以及KIR的阶段性基因组序列；并在3个猕猴物种中建立Fc伽马受体(FCGR)基因复合体的阶段性基因组序列。