ANTI-IDIOTYPE ANTIBODY APPROACH FOR AN HIV VACCINE

在这项研究中，我们建议继续开发一种抗独特型(抗id) -基于引出和/或促进广泛中和的战略 抗艾滋病毒抗体。这种方法的原理是基于 以抗-id作为抗原替代物的克隆型刺激 刺激B细胞库中特定元素的尝试 人类。在这项研究的第一阶段，鉴定了一种抗id单抗(3C9) 在免疫活性中诱导广谱中和抗gp12O抗体 猴子。我们的研究将扩展到确定3C9对 提高广谱中和抗gp120抗体效价。这一目标 将通过确定3C9在测试时的免疫原性实现 HIV感染者和gp120免疫猴子。同时，我们的 将继续努力开发新的抗id单抗，这种单抗可能优于 3C9在预防和治疗方面的潜力 疫苗。我们将产生抗id单抗，它与大多数 HIV感染者血清中普遍存在的广谱中和抗体 个人和接种疫苗的志愿者。这些抗id单抗将被测试 以确定它们是否有能力诱导和促进 幼猴和经gp120免疫的食蟹猴的抗gp120效价。通过 将这些结果与3C9的结果进行比较，我们将定义新的抗id单抗 用于临床研究。在实践中，抗id单抗可以用作 艾滋病毒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.