ATHE ANTI-IDIOTYPE ANTIBODY APPROACH FOR AN HIV VACCINE

在本研究中，我们建议继续开发一种抗独特型（抗ID） 基于基础的战略，以引出和（或）加强广泛中和 抗HIV抗体。 这种方法的原理是基于 利用抗ID作为抗原替代物的克隆型刺激， 试图刺激B细胞库的特定元件， 人类 在本研究的I期，鉴定了一种抗id单克隆抗体（3C9）， 在免疫小鼠中诱导广泛中和的抗gp12O抗体， 猴子 我们的研究将扩展到确定3C9的效用， 增强广泛中和的抗gp12O抗体的滴度。 这一目标 将通过测定3C9的免疫原性来实现， HIV感染者和gp120免疫猴。 同时，我们的 将继续努力开发新的抗id单克隆抗体， 3C9作为预防和治疗药物的潜力 疫苗。 我们将产生抗id单克隆抗体， HIV感染者血清中普遍存在的广泛中和抗体 接种疫苗的志愿者。 这些抗id单克隆抗体将被测试 以确定它们是否能够诱导和促进 未处理和gp12O致敏食蟹猴中的抗gp12O滴度。 通过 将这些结果与3C9的结果进行比较，我们将确定新的抗id单克隆抗体 用于临床研究。 在实践中，抗id单克隆抗体可以用作 HIV+个体的治疗和预防性疫苗， gp120免疫。

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.