HIGHLY EFFECTIVE CONTROL OF AIDS VIRUS CHALLENGE IN MACAQUES

高效控制猕猴中的艾滋病病毒挑战

• 批准号: 8358058
• 负责人: Preston A Marx
• 金额: $ 5.78万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358058
• 关键词: Animals; Antibodies; CD8B1 gene; Funding; Gagging; Genome; Goals; Grant; HIV; Immune system; Immunity; Infection; Macaca; Macaca mulatta; Monitor; Monkeys; National Center for Research Resources; Plasma; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Rest; SIV; Source; Techniques; Testing; United States National Institutes of Health; Vaccinated; Vaccination; Vaccines; Vesicular stomatitis Indiana virus; Viral; Viral Load result; Viral load measurement; Virus; Virus Diseases; Work; cost; in vivo

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. Six Rhesus macaques (Macaca mulatta) previously vaccinated with VSV/SFV E660 and challenged with SIVsmE660 were treated with anti-CD8 antibody to perform in vivo CD8 depletions in July 2010 (290 days after the original viral challenge). The four animals that completely resisted infection had plasma virus loads that remained undetectable after CD8 depletion further supporting the idea of sterilizing immunity in these animals. The two animals that resolved their SIV infections had a resurgence of viral infection with peak viral loads slightly higher than those seen previously (5.5 and 6.7 log copies/ml after depletion versus 3.9 and 5.8 log copies/ml previously) in these two monkeys. To further test if the protection afforded by the original vaccination is long lasting and if the immune system can be re-activated with an additional vaccination after a long period of rest, five animals protected from the original viral challenge will be re-immunized and re-challenged in the coming year. All animals will continue to be monitored to follow the progression of infection or lack thereof. Additionally in this study we are utilizing the single genome analysis (SGA) technique to a) to characterize Env of the SIVsmE660 viral challenge stock-we have finished sequencing and calculated the stock diversity of the challenge E660 swarm; and b) to characterize the founder viruses from rhesus macaques vaccinated with VSV vaccines and challenged intra-rectally. The goal is to compare and contrast the founder viruses Env sequences originating from animals vaccinated with VSV-HA vaccine from the two animals that showed partial protection-with VSV-E660-Gag-Env vaccine. This work is currently in progress.

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。 先前以VSV/SFV E660疫苗接种并接受SIVSME660挑战的六个恒河猕猴（Macaca Mulatta）接受了抗CD8抗体的治疗，以在2010年7月在Vivo CD8耗竭中进行（最初的病毒挑战后的290天）。 完全抵抗感染的四只动物具有血浆病毒载荷，在CD8耗竭后仍无法检测到，进一步支持了这些动物中免疫力的概念。 解决其SIV感染的两种动物的病毒感染的复发性峰值病毒载量略高于这两只猴子在耗尽后与3.9和3.9和5.8 log Copies/ml之后（5.5和6.7 log Copies/ml）的略高。 为了进一步测试原始疫苗接种提供的保护是否持久，如果长期休息后可以通过额外的疫苗接种将免疫系统重新激活，那么五只动物免受原始病毒挑战的保护，将在来年重新免疫并重新挑战。 所有动物将继续受到监测，以遵循感染的进展或缺乏感染的进展。 此外，在这项研究中，我们利用单个基因组分析（SGA）技术来表征SIVSME660病毒挑战的ENV，我们已经完成了测序，并计算了挑战E660群的库存多样性； b）表征来自用VSV疫苗接种的恒河猕猴的创始人病毒，并在直肠内挑战。 目的是比较和对比源自两种动物的VSV-HA疫苗的动物的创始人病毒ENV序列，这些动物显示出与VSV-E660-GAG-ENV疫苗的部分保护。目前正在进行这项工作。