A Max-Ad Vaccine for Mucosal Immunity to HIV

一种针对 HIV 粘膜免疫的 Max-Ad 疫苗

• 批准号: 6402992
• 负责人: Sybille L Sauter
• 金额: $ 20万
• 依托单位: CORAUTUS GENETICS, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2003-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6402992
• 关键词: AIDS vaccines; Adenoviridae; cellular immunity; colony stimulating factor; dendritic cells; gene delivery system; genetic transduction; laboratory mouse; mucosal immunity; vaccine development; vector vaccine; virus protein

DESCRIPTION (Provided by Applicant): To date there is no effective HIV vaccine available. Development of a beneficial HIV vaccine has been challenging due to the high mutation rate of the virus, in particular the envelope protein. Many of the 25 or more different HIV vaccines now in clinical trials target the envelope protein in an effort to raise an antibody response to that protein. New insight into effective anti-viral vaccines has focused attention on eliciting cellular immune responses. In addition, mucosal immunity to HIV is desirable for an effective HIV vaccine, since mucosal tissues are the common sites of initial infection. The vaccine being developed by GenStar targets these two issues by the inclusion of the HIV components known to elicit the best cellular immune responses and the ability of adenovirus to produce excellent mucosal immunity. GenStar's proprietary adenoviral vector, Max-Ad, is particularly suited for this approach, since it is a gutless adenovirus with a very large insert capacity. This capacity not only allows the inclusion of multiple HIV components but also the gene for the immunostimulatory cytokine, GM-CSF. In addition, this virus offers efficient transduction of most cells including dendritic cells, excellent high titer large-scale production, and the lack of synthesis of any adenoviral proteins. In the proposed studies we intend to determine the ability of a Max-Ad/HIV vaccine to elicit cellular immune responses to HIV through mucosal delivery. PROPOSED COMMERCIAL APPLICATION: HIV is a world-wide health problem with over 30 million people infected and 15,000 new cases of HIV infections diagnosed each day. Clearly, a prophylactic vaccine for this infectious disease is urgently needed and would produce significant financial and social returns. The potential for effective immunization via a mucosal route such as intranasal spray is particularly attractive in view of the large population at risk and the ease of administration.

描述(申请人提供)：到目前为止还没有有效的艾滋病毒疫苗 可用。开发一种有益的艾滋病毒疫苗一直具有挑战性，因为 病毒的高突变率，特别是包膜蛋白。许多 在目前正在进行临床试验的25种或更多不同的艾滋病毒疫苗中， 包膜蛋白，以努力提高对该蛋白的抗体反应。 对有效抗病毒疫苗的新见解将注意力集中在 引发细胞免疫反应。此外，粘膜对艾滋病毒的免疫力是 对于有效的艾滋病毒疫苗来说是可取的，因为粘膜组织是常见的 初次感染的地点。 Genstar正在开发的疫苗针对这两个问题 包含已知可诱导最好的细胞免疫的艾滋病毒成分 对腺病毒的反应和产生出色的粘膜免疫的能力。 Genstar的专有腺病毒载体Max-Ad特别适合于 这种方法，因为它是一种带有非常大插入物的无胆腺病毒 容量。这一能力不仅允许包括多种艾滋病毒 不仅是免疫刺激细胞因子GM-CSF的基因。在……里面 此外，这种病毒可以有效地转导大多数细胞，包括 树突状细胞，优良的高滴度规模化生产，和缺乏 任何腺病毒蛋白的合成。在拟议的研究中，我们打算 确定MAX-Ad/HIV疫苗诱导细胞免疫的能力 通过粘膜递送对艾滋病毒的反应。 建议的商业应用： 艾滋病毒是一个世界性的健康问题，每天有3000多万人感染，新诊断的艾滋病毒感染病例为15,000例。显然，迫切需要一种针对这种传染病的预防性疫苗，并将产生巨大的经济和社会回报。考虑到大量处于危险中的人群和易于管理，通过鼻腔喷雾等粘膜途径进行有效免疫的潜力特别有吸引力。