HIV li-Key/Peptide Vaccine

HIV 关键/肽疫苗

• 批准号: 6443099
• 负责人: MINZHEN XU
• 金额: $ 30.18万
• 依托单位: ANTIGEN EXPRESS, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-15 至 2003-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6443099
• 关键词: AIDS vaccines; MHC class II antigen; antigen antibody reaction; human immunodeficiency virus; invariant chain; laboratory mouse; lymphocyte proliferation; protein engineering; synthetic vaccines; vaccine development; virus antigen

DESCRIPTION: (Provided by Applicant) Antigen Express scientists have discovered that a segment of the Ii protein called Ii-Key, which acts at an allosteric site on one end of the antigenic peptide binding site on MHC Class II molecules, greatly enhances the binding of a tethered epitope. Linkage of such Ii-Key with a MHC class II-restricted epitope in a hybrid enhances the potency of presentation of the epitope >200 times, in vitro with murine and human assays, inducing a TH1 pattern of cytokine release. We propose to test such compounds with HIV MHC class II-restricted epitopes to expand CD4+ immunity and memory toward enhancing efficacy of HIV CTL peptide vaccines, the safest approach to HIV vaccination. We will: 1) design and synthesize several Ii-Key/HIV class II epitope hybrids according to our established methods; 2) test in mice the potencies of these hybrids in terms of T helper cell proliferation and the induction of neutralizing antibody against class II-restricted HIV epitope; and 3) design and synthesize an Ii-Key/class II epitope/CTL epitope double hybrid according to the data of 2); and then test the vaccine efficacy of this double hybrid in CTL induction. Our experiments will lead to a very potent HIV peptide vaccine. In a Phase II program the efficacy of such hybrids will be tested in higher primates and man. PROPOSED COMMERCIAL APPLICATION: Ii-Key/HIV peptide vaccine strategy will result in a very potent HIV peptide vaccine, the safest HIV vaccine. This entirely synthetic vaccine can be manufactured in a large scale and be given to those at high risk of HIV infection.

描述：（由申请人提供）Antigen Express科学家发现 Ii蛋白质中一个叫做Ii-Key的片段， MHC II类抗原肽结合位点一端的位点 分子，极大地增强了拴系表位的结合。这种联系 在杂交体中具有MHC II类限制性表位的Ii-Key增强了 表位呈递>200倍，在体外用鼠和人 测定，诱导细胞因子释放的TH 1模式。我们建议测试这种 具有HIV MHC II类限制性表位的化合物，以扩大CD 4+免疫力， 记忆朝向增强HIV CTL肽疫苗的功效，最安全 艾滋病疫苗接种。我们将：1）设计和合成几个 根据我们建立的方法的Ii-Key/HIV II类表位杂合体; 2） 在小鼠中测试这些杂交体在T辅助细胞方面的效力， 增殖和诱导抗类 II-限制性HIV表位;和3）设计和合成Ii-Key/II类 表位/CTL表位双杂交;然后测试 该双杂交体在CTL诱导中的疫苗效力。我们的实验 将导致一种非常有效的艾滋病毒肽疫苗。在第二阶段计划中， 将在高等灵长类动物和人类中测试这种杂交体的功效。 拟定商业应用： Ii-Key/HIV肽疫苗策略将产生非常有效的HIV肽疫苗， 最安全的HIV疫苗这种完全合成的疫苗可以大规模生产。 艾滋病病毒感染的风险很高。