HIV li-Key/Peptide Vaccine

描述：(由申请者提供)抗原快递科学家发现 II蛋白的一段叫做II-key，它在变构时起作用 MHC II类分子抗原肽结合部位的一端 分子，极大地增强了拴系表位的结合。这样的链接 在杂交种中具有MHC II类限制性表位的II-Key增强了效力 表位&gt；200次与小鼠和人的体外呈现 检测，诱导TH1模式的细胞因子释放。我们建议测试这一点 具有HIV MHC II类限制性表位的化合物可扩大CD4+免疫和 记忆增强HIV CTL多肽疫苗的效力，最安全 艾滋病毒疫苗接种的方法。我们将：1)设计和综合几个 根据我们已建立的方法制备II-Key/HIV II类表位杂交物；2) 在小鼠身上测试这些杂交种的T辅助细胞的效力 抗CLASS中和抗体的增殖及诱导 II-限制性HIV表位；3)设计和合成II-key/类II 根据2)的数据进行表位/CTL表位双杂交，然后检测 该双杂交疫苗诱导CTL的效果。我们的实验 将导致一种非常有效的艾滋病毒多肽疫苗。在第二阶段计划中， 这种杂交的效果将在高等灵长类动物和人类身上进行测试。 建议的商业应用： II-Key/HIV多肽疫苗策略将产生一种非常有效的HIV多肽疫苗， 最安全的艾滋病毒疫苗。这种完全合成的疫苗可以大量生产 并提供给艾滋病毒感染高危人群。

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.