PASSIVE ANTIBODY PROTECTION IN SHIV CHALLENGE MODEL

SHIV 挑战模型中的被动抗体保护

• 批准号: 6934945
• 负责人: Thomas C. VanCott
• 金额: $ 9万
• 依托单位: ADVANCED BIOSCIENCE LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6934945
• 关键词: Macaca mulatta; antiviral antibody; dendritic cells; disease /disorder model; human immunodeficiency virus 1; humoral immunity; intravenous administration; monoclonal antibody; mucosa; mucosal immunity; neutralizing antibody; passive immunization; sexually transmitted diseases; simian immunodeficiency virus; vagina

DESCRIPTION (Adapted from the applicant's abstract) Passive administration of specific antibody can protect against disease caused by viruses such as polio, measles, rubella, varicella, hepatitis A and hepatitis B. While antibody alone may not protect against HIV-1 infection, the investigators hypothesize that pre-existing antibody in systemic and mucosal compartments may be an important component of protection against transmission of HIV-1. The lack of an animal challenge model for HIV-1 that readily supports replication of primary isolates and simulates the physiology of sexual HIV-infection has made it difficult to perform passive transfer studies that would elucidate humoral correlates of protection. An additional obstacle is that few available antibodies appear capable of potent neutralization of primary HIV-1 isolates. The investigators have recently demonstrated that three antibody reagents (a polyclonal HIVIG and human Mabs 2F5 and 2G12) each neutralize primary HIV-1 strains and together, display synergistic neutralizing activity. They propose to study the efficacy of passive administration of these antibodies (alone or in combination) in preventing macaque infection by a SHIV containing the HIV-1 envelope of a primary isolate (SHIV-89.6). Experiments will include intravenous and intravaginal challenge, and in-vivo protection will be correlated to measured levels of serum and mucosal HIV-specific antibody. Particular emphasis will be placed on the intravaginal challenge system as a model of sexual transmission of HIV-1. The main objectives are to evaluate the protective efficacy of passively transferred antibody and to understand the humoral immune correlates of protection. In addition, since genital tract dendritic cells are likely initial targets of HIV-1 infection, the investigators will perform neutralizing antibody assays using skin and blood derived dendritic cells as targets of HIV-1 infection. Specific Aim 1. Develop in-vitro assays that can measure antibody-mediated virus neutralization from serum and muscosal specimens using human dendritic cells as targets of HIV-1 infection. Specific Aim 2. Evaluate the in-vivo efficacy of passive administration of anti-HIV-1 antibody combinations in protection of rhesus macaques against intravenous and muscosal SHIV challenge. Specific Aim 3. Correlate in-vivo protection from SHIV challenge with serum and muscosal antibody levels.

描述 （根据申请人的摘要改编）被动管理特定 抗体可以预防由脊髓灰质炎等病毒引起的疾病， 麻疹，风疹，水痘，丙型肝炎和乙型肝炎。 研究人员假设仅可能仅防止HIV-1感染， 全身和粘膜隔室中先前存在的抗体可能是 防止HIV-1传播的重要组成部分。 缺乏 HIV-1动物挑战模型的复制 主分离株并模拟性HIV感染的生理学 很难进行被动转移研究，以阐明 保护的相关性。 另一个障碍是很少 可用的抗体似乎能够有效地中和 HIV-1分离株。 调查人员最近证明了三个 抗体试剂（多克隆Hivig和人mAb 2f5和2g12） 中和主要的HIV-1菌株，一起显示协同作用 中和活性。 他们建议研究被动的功效 在防止这些抗体（单独或组合）的给药 猕猴感染了含有原发性的HIV-1信封的SHIV 分离物（Shiv-89.6）。 实验将包括静脉和静脉内的实验 挑战，体内保护将与测量的水平相关 血清和粘膜HIV特异性抗体。 将特别重点放置 在阴道内挑战系统上，作为性传播模型 HIV-1。 主要目的是评估 被动转移抗体并了解体液免疫 保护的关联。 另外，由于生殖道树突状细胞 可能是HIV-1感染的初始靶标，研究人员将 使用皮肤和血液衍生的树突状进行中和抗体测定 细胞作为HIV-1感染的靶标。 特定目标1。开发可以测量抗体介导的体外测定 使用人树突状的血清和肌肉标本中和病毒中和 细胞作为HIV-1感染的靶标。 具体目的2。评估被动给药的体内功效 保护猕猴的抗HIV-1抗体组合 静脉和肌肉动湿挑战。 特定目的3。将维沃内保护防寒挑战与血清相关联 和肌肉抗体水平。

项目成果

Selective increases in HIV-specific neutralizing antibody and partial reconstitution of cellular immune responses during prolonged, successful drug therapy of HIV infection.

在艾滋病毒感染的长期、成功的药物治疗过程中，艾滋病毒特异性中和抗体的选择性增加和细胞免疫反应的部分重建。

• DOI: 10.1089/088922201300343708
• 发表时间: 2001
• 期刊: AIDS research and human retroviruses
• 影响因子: 1.5
• 作者: Kim,JH;Mascola,JR;Ratto-Kim,S;VanCott,TC;Loomis-Price,L;Cox,JH;Michael,NL;Jagodzinski,L;Hawkes,C;Mayers,D;Gilliam,BL;Birx,DC;Robb,ML
• 通讯作者: Robb,ML