DEVELOPMENT OF A LOW INOCULUM SHIV CHALLENGE MODEL

低接种量 SHIV 挑战模型的开发

• 批准号: 7562569
• 负责人: Silvija I Staprans
• 金额: $ 6.55万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562569
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; Animals; Computer Retrieval of Information on Scientific Projects Database; Consensus; Development; Dose; Event; Funding; Grant; HIV; Health Priorities; Human; Immunology; Infection; Institution; Intervention; Macaca; Measures; Modeling; Nature; Numbers; Prevention; Prevention strategy; Reproducibility; Research; Research Personnel; Resources; Simian Acquired Immunodeficiency Syndrome; Source; Testing; United States National Institutes of Health; Vaccines; Vagina; Viral; microbicide; model development; pre-clinical; simian human immunodeficiency virus; size; transmission process; virology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Development of an HIV-inhibiting microbicide is a health priority. Consensus exists that an effective microbicide may be feasible. Simian AIDS models can help guide the development and prioritization of HIV prevention strategies. However, current models may not provide realistic pre-clinical tests of HIV prevention efficacy. The viral inoculum sizes used to infect macaques exceed those that humans are exposed to, and may underestimate the efficacy of HIV preventions. The small inocula associated with most human HIV exposures, combined with the likely stochastic nature of early infection events, may even make HIV transmission particularly susceptible to intervention. This project brings together investigators with expertise in AIDS virology and immunology, simian AIDS model development, and the mathematical analysis of HIV transmission events, to develop a challenge model that better recapitulates HIV transmission. The model uses vaginal inoculation with low doses of a CCR5-utilizing SHIV. Overall hypotheses: 1) Low-dose inocula, applied repeatedly, will achieve experimental SHIV infection with enough reproducibility so that prevention efficacy studies could be performed; power analyses predict that the animal numbers required to demonstrate efficacy are similar to those used in current high-dose challenge models, and 2) A low-dose challenge model will provide a more sensitive, physiologically relevant measure of the efficacy of microbicides, vaccines or other preventions. Efficacy would be demonstrated by showing that an intervention increases the number of challenges required to achieve infection, compared to controls.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 抑制HIV的杀菌剂的发展是健康的重点。共识存在有效的杀菌剂可能是可行的。 Simian AIDS模型可以帮助指导HIV预防策略的发展和优先级。但是，当前的模型可能无法提供现实的HIV预防效果的临床前测试。用于感染猕猴的病毒接种大小超过了人类暴露的猕猴，并可能低估了HIV预防的疗效。与大多数人类艾滋病毒暴露有关的小接种物，再加上早期感染事件的随机性质，甚至可能使HIV传播特别容易受到干预。该项目汇集了具有艾滋病病毒和免疫学专业知识的研究人员，烟熏艾滋病模型开发以及对艾滋病毒传播事件的数学分析，以开发一种更好地概括艾滋病毒传播的挑战模型。该模型使用低剂量的CCR5利用SHIV的阴道接种。总体假设：1）反复应用的低剂量接种将实现实验性SHIV感染，并具有足够的可重复性，以便可以进行预防功效研究；功率分析预测，证明功效所需的动物数量与当前高剂量挑战模型中使用的动力相似，而2）低剂量挑战模型将提供对微生物，疫苗或其他预防措施疗效的更敏感，生理相关的度量。与对照组相比，通过证明干预措施增加了实现感染所需的挑战数量，将证明功效。