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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 开发抑制艾滋病毒的杀菌剂是健康优先事项。人们一致认为有效的杀微生物剂可能是可行的。猿猴艾滋病模型可以帮助指导艾滋病毒预防策略的制定和优先顺序。然而，当前的模型可能无法提供艾滋病毒预防功效的现实临床前测试。用于感染猕猴的病毒接种量超过了人类接触的病毒接种量，并且可能低估了艾滋病毒预防的功效。与大多数人类艾滋病毒暴露相关的小接种量，加上早期感染事件可能具有的随机性，甚至可能使艾滋病毒传播特别容易受到干预。该项目汇集了艾滋病病毒学和免疫学、猿猴艾滋病模型开发以及艾滋病毒传播事件数学分析方面的专业知识的研究人员，以开发一个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利用 CCR5 的 SHIV 进行阴道接种。总体假设：1）低剂量接种，反复应用，将实现具有足够重复性的实验性SHIV感染，以便进行预防效果研究；功效分析预测，证明功效所需的动物数量与当前高剂量攻击模型中使用的动物数量相似，并且 2) 低剂量攻击模型将为杀菌剂、疫苗或药物的功效提供更灵敏、生理相关的测量方法。其他预防措施。与对照相比，干预措施增加了实现感染所需的挑战数量，从而证明了其有效性。