COXSACKIEVIRUSES AS CHIMERIC HIV VACCINE VECTORS

柯萨奇病毒作为嵌合 HIV 疫苗载体

• 批准号: 6374410
• 负责人: STEVEN M TRACY
• 金额: $ 21.9万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6374410
• 关键词: AIDS vaccines; Coxsackievirus; HIV envelope protein gp120; human immunodeficiency virus 1; interleukin 2; laboratory mouse; recombinant virus; vaccine development; vector vaccine

DESCRIPTION: (Adapted from Applicant's Abstract) Effective anti-HIV vaccines remain elusive while HIV infection rates are increasing. A key attribute of a successful anti-HIV vaccine formulation should be the ability to provide active, protective anti-HIV antibodies (including mucosal) and CMI responses. Human enteroviruses are excellent vaccines: like the closely related polioviruses, infection by any of the six group B coxsackieviruses (CVB1-6) generate life-long T (helper and cytotoxic) and B (including mucosal) cell anti-CVB type specific immunities in humans. We hypothesize that chimeric CVB can both express antigenic HIV-1 polypeptides and elicit protective anti-HIV-1 humoral and cellular immune responses in experimentally inoculated mice. The testing of this hypothesis is the objective of this proof-of-concept R21 grant proposal. Two specific aims of the proposal are proposed to meet this objective, experiments for which will be carried out concurrently. We will: [1] Determine the extent to which HIV-1 gp120 V3 loop region antigens are presented to the immune system during replication of the chimeric CVB3 strain in mice. CVB3 strains that express V3 loop containing gp120 polypeptides will be characterized in cell cultures and mice for replication and immunogenicity. [2] Investigate whether the murine host immune response against the gp120 antigen is augmented through the co-expression of murine IL-2 (mIL-2) linked to the gp120 polypeptide. Murine IL-2 will be expressed with a gp120 polypeptide as a fusion protein to determine the extent to which mIL-2 affects the murine immune responses to the antigen in comparison to a control CVB3 vector expressing just the gp120 fragment. Our long-term goal is the development of a chimeric CVB-based vaccine vector system for prophylactic, and possibly therapeutic, uses against HIV infection. Results from this proof-of-principle proposal will test feasibility within an HIV framework.

描述：（改编自申请人的摘要）有效的抗HIV疫苗 在艾滋病毒感染率上升时保持难以捉摸。一个关键属性 成功的抗HIV疫苗配方应成为提供的能力 主动保护性抗HIV抗体（包括粘膜）和CMI反应。 人肠病毒是极好的疫苗：像密切相关的疫苗 脊髓灰质炎，六组Coxsackievievieviruses感染（CVB1-6） 生成终身t（辅助和细胞毒性）和B（包括粘膜）细胞 人类的抗CVB类型特异性免疫。我们假设嵌合CVB 可以表达抗原HIV-1多肽并引起保护性抗HIV-1 实验接种小鼠的体液和细胞免疫反应。这 该假设的检验是此概念证明R21授予的目的 提议。提出了提案的两个具体目标来满足这一目标 客观，将同时进行实验。我们将：[1] 确定HIV-1 GP120 V3环区域抗原的程度 在小鼠中复制嵌合CVB3菌株时进行免疫系统。 表达含有GP120多肽的V3环的CVB3菌株将是 在细胞培养物和小鼠中以复制和免疫原性为特征。 [2] 调查鼠宿主对GP120抗原的免疫反应是否 通过与鼠有关的鼠IL-2（MIL-2）共表达与 GP120多肽。鼠IL-2将用GP120多肽作为一个 融合蛋白确定MIL-2影响鼠免疫的程度 与对照CVB3矢量相比，对抗原的反应公正 GP120片段。我们的长期目标是嵌合的发展 基于CVB的预防性疫苗媒介系统，可能是治疗性的 用于抗HIV感染的用途。此原理证明的结果将 在HIV框架内测试可行性。