THE ANTI-ALPHA-4/BETA-7 MONOCLONAL ANTIBODY PROJECT

抗 ALPHA-4/BETA-7 单克隆抗体项目

• 批准号: 8357511
• 负责人: Aftab A. Ansari
• 金额: $ 5.95万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357511
• 关键词: Acute; Affect; Attention; CD4 Positive T Lymphocytes; Cells; Chemokine (C-C Motif) Receptor 5; Chronic; Control Animal; Crohn' s disease; Funding; Future; Gastrointestinal tract structure; Grant; HIV; Immune response; Immunology; Infection; Inflammatory; Integrins; Journals; Lymphatic; Macaca mulatta; Monkeys; Monoclonal Antibodies; National Center for Research Resources; Organ; Pilot Projects; Primates; Principal Investigator; Research; Research Infrastructure; Resources; SIV; Site; Source; Syndrome; United States National Institutes of Health; Viral; Virus; cost; novel therapeutics; trafficking

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. One of the earliest organs affected by HIV and SIV infection is the GI tract. Moreover, the bulk of viral replication occurs in this compartment leading to rapid and permanent elimination of CD4+ T cells, in particular those co expressing the viral co-receptor CCR5. What is not clear to date is whether the continuous viral replication requires a constant influx of new CD4 targets or not, which would open a novel therapeutic vista by blocking traffic of potential target cells to the gut. Among the molecules dictating traffic to the gut the heterodimeric integrin ¿4¿7 has gained particular attention especially in the therapy of gut inflammatory syndromes such as IBD, UC and Crohn's Disease. We have pre-treated 4 rhesus macaques with a primatized monoclonal antibody specific to ¿4¿7prior to infection with SIVmac239 SIV replication and immune responses to the virus were compared in these monkeys and control animals given SIV only. Blocking cell traffic to the gut resulted in profound differences in the dynamic of the acute SIV infection lowering and delaying the peak of acute SIV replication and causing a shift of the main replication site from the gut to central lymphatic organs. Results of this pilot study have been accepted in the Journal of Immunology. Future analyses will investigate prolonged blockade of cell traffic to the gut during chronic infection and after mucosal challenge.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 受艾滋病毒和SIV感染影响的最早的器官之一是胃肠道。此外，大部分病毒复制发生在此室中，导致快速，永久消除CD4+ T细胞，特别是那些表达病毒共受体CCR5的细胞。迄今为止尚不清楚的是，连续病毒复制是否需要新的CD4靶标的持续影响，这将通过阻止潜在靶细胞到肠道的流量来打开一种新型的治疗远景。在指示肠道流量的分子中，异二聚体整合素€4已引起了人们的特别关注，尤其是在肠道炎性综合症的治疗中，例如IBD，UC和Crohn病。我们已经预处理了4个恒河猕猴，并与SIVMAC239 SIV复制感染之前，在感染SIVMAC239 siv复制和对病毒的免疫反应之前，仅在给定SIV的动物中比较了对病毒的免疫反应。阻塞肠道的细胞流量导致急性SIV感染的动态降低并延迟急性SIV复制的峰值，并导致主复制位点从肠道到中央淋巴器官的转移。该试点研究的结果已在《免疫学杂志》中接受。未来的分析将在慢性感染期间和粘膜挑战后长期研究对肠道的细胞流量的长时间封锁。