ATHE ANTI-IDIOTYPE ANTIBODY APPROACH FOR AN HIV VACCINE

HIV 疫苗的抗独特型抗体方法

• 批准号: 3506179
• 负责人: KANDASAMY HARIHARAN
• 金额: $ 25万
• 依托单位: IDEC PHARMACEUTICALS CORPORATION
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-15 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3506179
• 关键词: AIDS vaccines; B lymphocyte; HIV envelope protein gp120; HIV infections; Macaca fascicularis; active immunization; antibody neutralization test; antiidiotype antibody; antiserum; antiviral antibody; chemoprevention; human immunodeficiency virus; human subject; humoral immunity; laboratory mouse; microorganism disease chemotherapy; monoclonal antibody; neutralizing antibody; radioimmunoassay; technology /technique development; tissue /cell culture

In this study we propose to continue to develop an anti-idiotype (anti-id) -based strategy for eliciting and/or boosting broadly neutralizing antibodies against HIV. The principle of this approach is based on clonotypic stimulation which utilizes anti-id as surrogate for antigen in an attempt to stimulate specific elements of the B cell repertoire in humans. In phase I of this study, one anti-id Mab (3C9) was identified which induced broadly neutralizing anti-gp12O antibodies in immunonaive monkeys. Our studies will be extended to identify the utility of 3C9 to boosting titers of broadly neutralizing anti-gp12O antibodies. This aim will be achieved by determining the immunogenicity of 3C9 when tested in HIV-infected individuals and gp120 immune monkeys. In parallel, our efforts will continue to develop new anti-id Mabs which may be superior to 3C9 with respect to their potential as both prophylactic and therapeutic vaccines. We will generate anti-id Mabs which interact with the most prevalent, broadly neutralizing antibodies in the sera of HIV-infected individuals and vaccinated volunteers. These anti-id Mabs will be tested to determine whether they are capable of inducing and boosting the anti-gp12O titer in naive and gp12O primed cynomolgus monkeys. By comparing these results with that of 3C9, we will define new anti-id Mabs for clinical studies. In practice, the anti-id Mabs could be used as a therapy for HIV+ individuals and a prophylactic vaccine when combined with gp12O immunizations.

在这项研究中，我们建议继续开发抗IDiotype（抗ID） - 基于引发和/或增强广泛中和的策略 抗艾滋病毒的抗体。 这种方法的原则是基于 克隆型刺激，利用抗ID作为替代抗原的抗原 试图刺激B细胞库中的特定元素 人类。 在本研究的第一阶段，鉴定了一个抗ID mAb（3C9） 它诱导了免疫剂中广泛中和抗GP12O抗体 猴子。 我们的研究将扩展以确定3C9的效用 促进广泛中和抗GP12O抗体的滴度。 这个目标 通过确定3C9的免疫原性来实现 HIV感染的个体和GP120免疫猴子。 并行，我们的 努力将继续发展新的抗ID mAB，可能优于 3C9关于它们作为预防和治疗的潜力 疫苗。 我们将产生与最多相互作用的抗ID mAB 流行的，广泛中和抗体的抗体 个人和接种式志愿者。 这些抗ID mAB将被测试 确定它们是否能够诱导和增强 天真和gp12o的抗GP12O滴度。 经过 将这些结果与3C9的结果进行比较，我们将定义新的抗ID mAB 用于临床研究。 实际上，抗ID mAB可以用作 与HIV+个体和预防性疫苗的治疗 GP12O免疫。