MULTI EPITOPE HIV PEPTIDE AND V1/V2 PROTEIN VACCINES

多表位 HIV 肽和 V1/V2 蛋白疫苗

• 批准号: 2627924
• 负责人: Arye Rubenstein
• 金额: $ 47.06万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-15 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2627924
• 关键词: AIDS vaccines; synthetic vaccines; vaccine development; virus antigen; virus protein

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.

这个疫苗项目由一组互动的研究人员组成， 长期致力于艾滋病疫苗研究议程。 我们的V3环和gp 41肽与PPD和M缀合。结核 (TB)衍生的蛋白质载体在其他中和中 在人类和动物中的主要分离株的抗体。新守恒 V1/V2区的糖蛋白似乎也诱导广泛的 中和 该计划的总体目标是利用我们的经验来开发： 1)改进的预防性肽AIDS疫苗，包括但不限于 V3环和gp 41鸡尾酒我们的肽疫苗的灵活性 发展将使我们能够迅速和廉价地纳入新的 表位，如与HIV-1共受体相关的表位。 2)品特博士将通过结合到 PPD介导gp 120的V1/V2结构域的高度保守表位 有效中和嗜M性原代HIV分离株。 3)Goldstein博士的人类CD 4/CCR 5转基因小鼠将作为一种在 所有疫苗构建体的体内模型。此外，HIV感染的SCID- hu小鼠（核心）将提供体内系统来测试生物学特性。 在动物和人类中产生的中和抗体的功能。 这一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型。 在有限的临床试验中，PPD V3五肽结合疫苗 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 Javadian，我们将评估多表位V3，gp 41 肽-PPD-缀合物疫苗以诱导中和抗体， 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， ThereGuide和瑞士血清和疫苗研究所（SSVI）编制GLP 可用于临床试验的疫苗。临床试验最初将 继续出国（以色列;巴西），那里很容易有一个大型PPD+队列 available.美国未来的研究将采用NIAID计划进行设计 工作人员