Oral Vaccine-Induced Cellular Immunity Against HIV-1

口服疫苗诱导的针对 HIV-1 的细胞免疫

• 批准号: 6408853
• 负责人: David Michael Hone
• 金额: $ 37.13万
• 依托单位: UNIVERSITY OF MD BIOTECHNOLOGY INSTITUTE
• 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/6408853
• 关键词: AIDS vaccines; CD4 molecule; CD8 molecule; HIV envelope protein gp120; HIV infections; Salmonella; active immunization; antigen antibody reaction; biological models; cellular immunity; chemokine; cholera toxin; enzyme linked immunosorbent assay; growth factor; human immunodeficiency virus 1; humoral immunity; immunomodulators; immunoregulation; laboratory mouse; mucosal immunity; nonhuman therapy evaluation; oral administration; suppressor T lymphocyte; tissue /cell culture; vaccine development; vector vaccine

DESCRIPTION (Provided by Applicant): The long-term goal of this proposal is to develop a Salmonella HIV-1 DNA vaccine vector that elicits humoral and cell-mediated immune responses against HIV-1, both in the mucosal and systemic immune compartments. Rationale for the development of these vectors stems from an increasing body of evidence indicating that mucosal immunity is likely to play a significant role in protection against sexually acquired HIV-1. Furthermore, although it is possible to boost mucosal responses with parenteral immunogens, induction of strong mucosal immune responses requires mucosal priming. In this vein, we have shown that intragastric vaccination with a Salmonella Env DNA vaccine vector generates Env-specific CD8+ T cells, in both mucosal and systemic lymphoid tissues. By contrast, intramuscular vaccination with the Env DNA vaccine only induces a CD8+ T cell response to Env in systemic lymphoid tissues. The central hypothesis of this proposal, therefore, is that Salmonella HIV-1 DNA vaccine vectors are more effective at priming mucosal immune responses to HIV-1 antigens, than parenteral HIV-1 DNA vaccines. We will address our central hypothesis and reach the long-term goal of this proposal by completing the following specific aims: 1. To construct DNA vaccines that co-express an HIV-1 antigen and a mucosal adjuvant; 2: Identify a Salmonella HIV-1 DNA vaccine that elicits durable humoral and cellular responses to HIV-l in the mucosal and systemic immune compartments; 3. To determine whether preexisting immunity against Salmonella reduces the immunogenicity of Salmonella HIV-1 DNA vaccine vectors; 4: To measure the immunogenicity of an array of prime-boost vaccination protocols using selected Salmonella vector constructs developed in aims 1 through 3. Overall, we believe that the studies proposed herein will further advance this vector system toward widespread clinical application in developing and developed countries.

描述（由申请人提供）：该提案的长期目标是 开发出一种HIV-1 DNA疫苗载体，该疫苗引起体液和 细胞介导的针对HIV-1的免疫反应，无论是在粘膜和全身性的 免疫室。这些媒介的发展基本原理源于 越来越多的证据表明粘膜免疫可能可能 在保护性获得的HIV-1中发挥重要作用。 此外，尽管有可能通过肠胃外增强粘膜反应 免疫原子，诱导强粘膜免疫反应需要粘膜 启动。在这种脉中，我们已经表明，胃内疫苗接种 沙门氏菌ENV DNA疫苗载体在两者中都会产生ENV特异性CD8+ T细胞 粘膜和全身性淋巴组织。相比之下，肌内疫苗接种 使用ENV DNA疫苗仅诱导系统性的CD8+ T细胞对ENV的反应 淋巴组织。因此，该提议的核心假设是 HIV-1沙门氏菌DNA疫苗载体在启动粘膜方面更有效 与肠胃外HIV-1 DNA疫苗相比，对HIV-1抗原的免疫反应。我们将 解决我们的中心假设，并实现该提议的长期目标 完成以下特定目的：1。构建DNA疫苗 共表达HIV-1抗原和粘膜佐剂； 2：确定沙门氏菌 HIV-1 DNA疫苗会引起对HIV-L的持久体液和细胞反应 在粘膜和全身免疫室中； 3。确定是否 预先存在针对沙门氏菌的免疫力降低了免疫原性 HIV-1 DNA疫苗载体； 4：测量 使用选定沙门氏菌载体的一系列促进疫苗接种方案阵列 在目标1到3中开发的结构。总体而言，我们认为研究 本文提出的将进一步推进该矢量系统 在发展中国家和发达国家中的临床应用。