An Adenoviral-Based Mucosal Vaccine for AIDS

一种基于腺病毒的艾滋病粘膜疫苗

• 批准号: 6798879
• 负责人: GIRIJA MURALIDHAR
• 金额: $ 29.33万
• 依托单位: LA JOLLA INST FOR MOLECULAR MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6798879
• 关键词: AIDS vaccines; Adenoviridae; HIV infections; antigen presenting cell; cellular immunity; enzyme linked immunosorbent assay; helper T lymphocyte; immune response; laboratory mouse; mucosal immunity; neutralizing antibody; polyethylene glycols; vaccine development; vector vaccine; viral vaccines; virus envelope; western blottings

DESCRIPTION (provided by applicant): AIDS is a worldwide health problem with 36 million people infected with HIV and estimated 5 million new infections occurring per year. These numbers indicate the need for a prophylactic vaccine to prevent the further spread of the disease. Despite tremendous efforts in AIDS vaccine research, traditional methods of vaccine development have failed to produce an effective vaccine for HIV infection. Recent vaccine efforts have focused on eliciting cellular immune responses directed against structural proteins of HIV instead/in addition to targeting humoral immune responses to the envelope. With that approach, adenoviral vector based vaccines have shown a great potential as vaccines for HIV in humans. Adenoviral vectors elicit strong innate immune responses, which greatly aid in inducing strong cellular immune responses. Moreover, adenoviruses are excellent as mucosal vaccines. However, one major drawback of adenoviral vaccines is prior immunity to adenoviruses in human, which could limit their efficacy. We propose to utilize a PEGylation technique to mask our Adeno-based AIDS vaccine vector, Ad/HIV, and test its efficacy in vivo. We propose to evaluate innate immune responses induced by the mucosal administration of PEGylated Ad/HIV (via intranasal route) and cellular immune responses (CTL and cytokine profiles) directed to HIV immunogen; gag encoded by the adenovector. In addition, we will determine both systemic and mucosal immune responses generated to PEGylated Ad/HIV. We will test the efficacy of PEGylated Ad/HIV both in naive mice and in mice with pre-existing immunity to adenoviruses. The results from this study will provide the groundwork for the development of a highly effective mucosal AIDS vaccine that can be repeatedly administered to patients with high efficacy.

描述（由申请人提供）：艾滋病是一个世界性的健康问题，有 3600 万人感染艾滋病毒，估计每年有 500 万人感染艾滋病毒。这些数字表明需要预防性疫苗来防止疾病的进一步传播。尽管在艾滋病疫苗研究方面付出了巨大努力，但传统的疫苗开发方法未能生产出有效的艾滋病毒感染疫苗。最近的疫苗研究重点是引发针对 HIV 结构蛋白的细胞免疫反应，而不是/除了针对包膜的体液免疫反应。通过这种方法，基于腺病毒载体的疫苗显示出作为人类艾滋病毒疫苗的巨大潜力。腺病毒载体引发强烈的先天免疫反应，这极大地有助于诱导强烈的细胞免疫反应。此外，腺病毒非常适合作为粘膜疫苗。然而，腺病毒疫苗的一个主要缺点是人类对腺病毒具有预先免疫力，这可能会限制其功效。 我们建议利用聚乙二醇化技术来掩盖我们的基于腺苷的艾滋病疫苗载体 Ad/HIV，并测试其体内功效。我们建议评估粘膜施用聚乙二醇化 Ad/HIV（通过鼻内途径）诱导的先天免疫反应和针对 HIV 免疫原的细胞免疫反应（CTL 和细胞因子谱）；由腺病毒载体编码的gag。此外，我们将确定对 PEG 化 Ad/HIV 产生的全身和粘膜免疫反应。我们将测试 PEG 化 Ad/HIV 在初始小鼠和预先具有腺病毒免疫力的小鼠中的功效。 这项研究的结果将为开发一种高效的粘膜艾滋病疫苗奠定基础，这种疫苗可以对患者重复注射，效果良好。