Assay/Measuring HIV-1 and SIV Antibody Neutralization

测定/测量 HIV-1 和 SIV 抗体中和

• 批准号: 6894151
• 负责人: CHRISTOS J PETROPOULOS
• 金额: $ 30.86万
• 依托单位: MONOGRAM BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6894151
• 关键词: animal tissue; antibody neutralization test; antiviral agents; biotechnology; clinical research; drug resistance; genetic library; genotype; human immunodeficiency virus 1; human tissue; neutralizing antibody; phenotype; polymerase chain reaction; simian immunodeficiency virus; technology /technique development; transfection /expression vector; virus envelope; virus genetics; virus infection mechanism; virus receptors

DESCRIPTION (provided by applicant): Recent strides in HIV-1 vaccine research have begun to define the roles of cellular and humoral immune responses and have renewed optimism that an effective prophylactic vaccine can be developed (Ho and Huang, 2002). It is anticipated that several vaccine candidates will be ready for large-scale evaluations in humans in the near future (2-5 years). In all likelihood, the development of a highly efficacious vaccine will be an iterative process in which lessons learned from early vaccine trials improve future generation vaccines. The evaluation of early candidates should help further clarify the protective roles of humoral (B-cell antibody) and cellular (cytotoxic T-cell) immune responses, and possibly identify other critical surrogate markers of protection. Once gleaned, this information can be directed toward the development of more potent and directed immunogens and delivery systems. At present, the HIV vaccine field is inadequately equipped to conduct the comprehensive analyses necessary to support ongoing and future vaccine efforts. In general, assays currently available to evaluate HIV-specific immune responses were developed for small research investigations and are not suited for the high volume sample testing necessary to support high throughput screening of potential immunogens, or large clinical efficacy trials. Such studies will require rapid, sensitive, and reliable assays with high-throughput testing capability. Furthermore, such systems must be amenable to pre-clinical investigations conducted in primate model systems, i.e. SIV/macaque. Recently, ViroLogic developed a novel cell-based infectivity assay that is capable of three distinct applications, (a) measuring the susceptibility of HIV-1 to entry inhibitor drugs, (b) determining co-receptor tropism and (c) detecting antibody neutralization. This SBIR-AT phase I proposal is focused on the further development of the antibody neutralization application. We intend to expand and enhance the capability of the neutralization assay, compile a large diverse specimen library comprised of functional HIV-1 envelope genes, and establish standard virus panels for the routine characterization of antibody responses.

描述（由申请人提供）：HIV-1疫苗研究的最新进展已开始确定细胞和体液免疫应答的作用，并重新乐观地认为可以开发有效的预防性疫苗（Ho和Huang，2002）。预计在不久的将来（2-5年），几种候选疫苗将准备好进行大规模的人体评价。极有可能，高效疫苗的开发将是一个反复的过程，从早期疫苗试验中吸取的经验教训将改进下一代疫苗。对早期候选者的评估应有助于进一步阐明体液（B细胞抗体）和细胞（细胞毒性T细胞）免疫应答的保护作用，并可能确定其他关键的保护替代标志物。一旦收集到这些信息，就可以直接用于开发更有效和定向的免疫原和递送系统。目前，艾滋病毒疫苗领域没有足够的能力进行必要的全面分析，以支持目前和今后的疫苗工作。一般而言，目前可用于评价HIV特异性免疫应答的检测方法是针对小型研究开发的，不适合支持潜在免疫原高通量筛选所需的大体积样本检测或大型临床疗效试验。这些研究将需要快速，灵敏，可靠的高通量检测能力的测定。 此外，此类系统必须适合在灵长类动物模型系统（即SIV/猕猴）中进行的临床前研究。最近，ViroLogic开发了一种新的基于细胞的感染性测定，能够用于三种不同的应用，（a）测量HIV-1对进入抑制剂药物的敏感性，（B）确定共受体向性和（c）检测抗体中和。该SBIR-AT I期提案的重点是抗体中和应用的进一步开发。我们打算扩大和提高中和试验的能力，编制一个大型的不同标本库的功能HIV-1包膜基因组成，并建立标准的病毒面板的抗体反应的常规表征。