ANTI-CD4 ANTIBODY AS THERAPEUTIC/PREVENTIVE HIV VACCINE

抗 CD4 抗体作为治疗/预防 HIV 疫苗

• 批准号: 3489229
• 负责人: CHANG-YUIL KANG
• 金额: $ 5万
• 依托单位: IDEC PHARMACEUTICALS CORPORATION
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3489229
• 关键词: AIDS vaccines; CD4 molecule; antiantibody; antibody neutralization test; disease /disorder prevention /control; enzyme linked immunosorbent assay; epitope mapping; hybridomas; immunological substance; laboratory rabbit; laboratory rat; monoclonal antibody

Attempts to make a practical HIV vaccine have so far been unsuccessful. Here, we propose using an anti-HIV receptor (CD4) antibody as an HIV vaccine to circumvent the current problems of HIV vaccine trials. The premise of our approach is based upon the assumption that certain anti-CD4 antibodies can structurally mimic the neutralizing epitope of gp120 and elicit neutralizing anti-gp120 antibodies. We will generate a panel of murine anti-CD4 MAbs and characterize them in vitro to identify candidates for gp120-mimicking antibodies by epitope mapping and in vitro virus neutralization assays. Based upon in vitro characterizations, anti-CD4 MAbs will be selected and evaluated in vivo to identify their potential utility in eliciting neutralizing anti-gp120 antibodies against various HIV isolates. For this, rabbits and rats will be immunized with anti-CD4 MAbs and the sera will be evaluated for neutralizing anti-gp120 antibodies by measurement of anti-gp120 titer in ELISA and virus neutralization assays using various HIV isolates. In phase 2, we will further evaluate the effect of anti-CD4 MAbs as an HIV vaccine in primates. At that time, protection experiments against viral infection will be performed.

到目前为止，制造实用的艾滋病毒疫苗的尝试还没有成功。 在这里，我们建议使用抗HIV受体(CD4)抗体作为HIV 疫苗以绕过目前艾滋病毒疫苗试验的问题。这个 我们方法的前提是假设某些抗CD4抗体 抗体可以在结构上模拟gp120的中和表位，并 诱导产生中和抗gp120抗体。我们将生成一个面板，其中 鼠抗CD_4单抗及其体外鉴定候选抗体 通过表位定位和体外病毒检测获得gp120模拟抗体 中和试验。基于体外特性，抗CD4 将在体内选择和评估单抗，以确定其潜力 诱导抗多种HIV中和性抗gp120抗体的应用 分离株。为此，将用抗CD4单抗免疫兔子和大鼠 并通过以下方法评估血清中和抗gp120抗体的能力 酶联免疫吸附试验和病毒中和试验中抗gp120滴度的测定 使用不同的艾滋病毒分离株。在第二阶段，我们会进一步评估 抗CD4单抗作为HIV疫苗在灵长类动物中的效果。当时， 将进行针对病毒感染的保护实验。