MULTI EPITOPE HIV PEPTIDE AND V1/V2 PROTEIN VACCINES

该疫苗项目由一组互动式调查人员组成 长期致力于艾滋病疫苗研究议程。 我们的V3环和gp41多肽与PPD和结核分枝杆菌结合 (TB)衍生蛋白载体在其他中和中诱导 在人类和动物中对初级分离株的抗体。新保守派 V1/V2区域的糖蛋白似乎也能诱导广泛的 中和。 该计划的总体目标是利用我们的经验来开发： 1)改进的预防性多肽艾滋病疫苗包括但不限于 V3循环和gp41鸡尾酒。我们的多肽疫苗的灵活性 开发将使我们能够快速且廉价地整合新的 与HIV-1共受体相关的表位。 2)品特博士将为这个项目增加一个新的维度 Gp120 V1/V2区高度保守的PPD表位 对嗜M的主要HIV分离株进行有效的中和。 3)戈尔茨坦博士的人类CD4/CCR5转基因小鼠将成为 所有疫苗构建的活体模型。此外，感染艾滋病毒的SCID- HU小鼠(CORE)将提供体内系统来测试生物学 中和动物和人类产生的抗体的功能。 这个合作项目的重点是预防性疫苗，但将 还利用治疗性疫苗接种作为预防性疫苗的模式。 PPD V3五肽结合疫苗的有限临床试验 在HIV PPD受试者中诱导高滴度的初级分离株中和 抗体和降低血浆病毒载量。与阿里博士合作 爪哇人，我们将评估多表位V3，gp41的潜力 多肽-PPD结合物疫苗诱导中和抗体和 减少卡介苗免疫的HIV黑猩猩的病毒载量。 该财团将继续与其商业伙伴合作， 指南和瑞士血清和疫苗研究所(SSVI)准备GLP 可用于临床试验的疫苗。临床试验最初将 继续留在国外(以色列；巴西)，那里有一大批PPD队列 可用。未来在美国的研究将与NIAID计划一起设计 工作人员。

This vaccine program is comprised of a group of interactive investigators with a long standing commitment to the AIDS vaccine research agenda. Our V3 loop and gp41 peptides conjugated to PPD and to M. tuberculosis (TB) derived protein carriers have induced among other neutralizing antibodies to primary isolates in humans and in animals. New conserved glycoproteins in the V1/V2 regions appear also to induce broad neutralization. The overall goal of this program is to exploit our experience to develop: 1) improved preventative peptide AIDS vaccines to include but not limited to the V3 loop and gp41 cocktails. The flexibility of our peptide vaccine development will allow us to rapidly and inexpensively incorporate new epitopes such as those related to HIV-1 co-receptors. 2) Dr. Pinter will add a new dimension to this program by conjugating to PPD highly conserved epitopes of the V1/V2 domain of gp120 which mediate potent neutralization of M tropic primary HIV isolates. 3) Dr. Goldstein's human CD4/CCR5 transgenic mouse will serve as an in vivo model for all vaccine constructs. In addition the HIV infected SCID- hu mice (core) will provide an in vivo system to test the biological function of neutralizing antibodies generated in animals and in humans. This collaborative project focuses on preventative vaccines but will utilize also therapeutic vaccination as a model for preventative vaccines. In limited clinical trials out PPD V3 pentapeptide conjugate vaccine induced in HIV+PPD+ subjects high titers of primary isolate neutralizing antibodies and reduced plasma viral loads. In collaboration with Dr. Ali Javadian, we will evaluate the potential of a polyepitopic V3, gp41 peptide-PPD-conjugate vaccine to induce neutralizing antibodies and to reduce viral loads in BCG immunized HIV+ chimps. This consortium will continue to collaborate with its commercial partners, ThereGuide and the Swiss Serum and Vaccine Institute (SSVI) to prepare GLP vaccine available for clinical trials. Clinical trials will initially continue abroad (Israel; Brazil) where a large PPD+ cohort is readily available. Future studies in the US will be designed with NIAID program staff.