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）：本提案的长期目标是 开发一种沙门氏菌HIV-1 DNA疫苗载体， 粘膜和全身的细胞介导的抗HIV-1免疫应答 免疫区室开发这些载体的理由来自于 越来越多的证据表明粘膜免疫可能 在预防性行为感染HIV-1方面发挥重要作用。 此外，尽管胃肠外给药可以增强粘膜反应， 免疫原，诱导强粘膜免疫应答需要粘膜 启动在这方面，我们已经表明，胃内接种一种 沙门氏菌Env DNA疫苗载体产生Env特异性CD 8 + T细胞， 粘膜和全身淋巴组织。相比之下，肌肉注射疫苗 Env DNA疫苗仅诱导全身性CD 8 + T细胞对Env的应答， 淋巴组织因此，这一建议的核心假设是， 沙门氏菌HIV-1 DNA疫苗载体在启动粘膜免疫方面更有效 免疫反应的HIV-1抗原比肠胃外HIV-1 DNA疫苗。我们将 解决我们的中心假设，并实现这一建议的长期目标， 完成以下具体目标：1.构建DNA疫苗， 共表达HIV-1抗原和粘膜佐剂; 2：鉴定沙门氏菌 HIV-1 DNA疫苗诱导的体液和细胞免疫应答 在粘膜和全身免疫区室中; 3.以确定是否 预先存在的对沙门氏菌的免疫力降低了 沙门氏菌HIV-1 DNA疫苗载体; 4：为了测量 使用选定沙门氏菌载体的一系列初免-加强疫苗接种方案 在目标1至3中发展的结构。总的来说，我们认为这些研究 本文提出的方法将进一步推进该载体系统向广泛应用的方向发展。 在发展中国家和发达国家的临床应用。