A NOVEL STRATEGY TO INDUCE NEUTRALIZING ANTIBODIES TO HIV

诱导 HIV 中和抗体的新策略

• 批准号: 8357710
• 负责人: Krishna K Murthy
• 金额: $ 2.54万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357710
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; Antibodies; Antigens; Blood donor; Boxing; CD4 Positive T Lymphocytes; Cell Count; Code; DNA; Development; Disease; Disease Progression; Dose; Event; Exposure to; Funding; GB virus C; Grant; HIV; HIV Infections; Human; Immune response; Immunity; In Vitro; Infection; Infection prevention; Macaca mulatta; Monitor; Monkeys; Monoclonal Antibodies; National Center for Research Resources; Neck; Outcome; Pilot Projects; Prevention; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Role; Source; Thinking; Time; United States National Institutes of Health; Vaccinated; Vaccines; Virus; cost; env Gene Products; neutralizing antibody; novel strategies; polyclonal antibody; simian human immunodeficiency virus

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Multiple vaccine strategies to induce protective immunity against HIV infection and prevention of progression to AIDS, have been unsuccessful as of to date. The current thinking is to look for " outside the box" approaches to overcome this bottle neck in developing an effective vaccine. We hypothesize that one such approach is to investigate the role of an envelope protein derived from an unrelated virus (GBV-C) as an immunogen that will induce broadly cross-reactive high titered neutralizing antibodies that will prevent infection in immunized rhesus monkeys following challenge with a SHIV isolate. GBV-C is prevalent in nearly 1% of blood donors in the US but is not associated with any diseases. Several studies have shown that exposure to GBV-C and HIV is associated with higher CD4+ T cell numbers, lower infection and prolonged survival times when compared with HIV infection alone. Those events appear to correlate with the development of antibodies to envelope protein of GBV-C and raise the possibility that such antibodies may modify HIV infection and disease progression. Recent studies have demonstrated that polyclonal or monoclonal antibodies to the envelope protein neutralized a broad panel of HIV isolates and a SHIV isolate in vitro. Therefore, we propose to conduct a proof -of -concept pilot study using rhesus monkeys that will be vaccinated with DNA coding for the envelope protein followed by booster doses of the envelope protein. The immunized monkeys will be monitored for the development of immune responses to the envelope protein and along with unvaccinated control monkeys will be challenged with a SHIV isolate to determine the outcome. It is anticipated that this strategy will provide important information toward the development of an effective vaccine for the prevention of HIV infection and or disease progression in humans.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 迄今为止，诱导针对HIV感染的保护性免疫和预防进展为AIDS的多种疫苗策略尚未成功。目前的想法是寻找“盒子外”的方法来克服开发有效疫苗的这一瓶颈。我们假设，这样的一种方法是调查的作用，来自一个无关的病毒（GBV-C）的包膜蛋白作为一种免疫原，将诱导广泛的交叉反应性高滴度中和抗体，将防止感染免疫恒河猴后的挑战与SHIV分离。GBV-C在美国近1%的献血者中流行，但与任何疾病无关。几项研究表明，与单独感染艾滋病毒相比，暴露于GBV-C和艾滋病毒与较高的CD 4 + T细胞数量，较低的感染和延长的生存时间有关。这些事件似乎与GBV-C包膜蛋白抗体的产生相关，并提高了这些抗体可能改变HIV感染和疾病进展的可能性。最近的研究表明，多克隆或单克隆抗体的包膜蛋白中和了广泛的面板的HIV分离株和SHIV分离株在体外。因此，我们建议使用恒河猴进行概念验证试点研究，这些恒河猴将接种编码包膜蛋白的DNA，然后接种加强剂量的包膜蛋白。 将监测免疫猴对包膜蛋白的免疫应答的发展，并将用SHIV分离株对沿着未接种对照猴进行攻毒，以确定结果。预计这一策略将为开发预防人类HIV感染和/或疾病进展的有效疫苗提供重要信息。