COMBINED VACCINE STRATEGIES FOR THE PREVENTION OF AIDS

预防艾滋病的联合疫苗策略

• 批准号: 6506522
• 负责人: DENNIS L PANICALI
• 金额: $ 42.88万
• 依托单位: THERION BIOLOGICS CORPORATION
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6506522
• 关键词: AIDS vaccines; human immunodeficiency virus; recombinant virus; vaccine development; vector vaccine

The long-term objective of this program is the development of effective vaccines against HIV using novel recombinant viral vectors. Toward this end, the goals of this proposal are to attain a better understanding of the protective immune responses against HIV and to design novel antigen configurations and improved vectors to elicit these protective immune responses. The combined projects of this program have five major specific aims: 1. Comparison of the immune responses against HIV in individuals that exhibit long-term non-progressive HIV infection with those that have normal progression of HIV infection. 2. Modification of HIV and SIV genes to enhance antigen presentation, insertion of these altered genes into poxvirus vectors, and assessment of these recombinant viruses in rodents. Such modifications are aimed at increasing protein processing, enhancing or redirecting intracellular transport, or exposing sequestered epitopes. Co-stimulatory molecules will be included to enhance cellular immune responses. 3. Expression of genes encoding potent antibodies to neutralize HIV. Genes encoding broadly neutralizing antibodies will be inserted into recombinant adeno-associated virus to deliver high levels of neutralizing antibodies to the circulation. 4. Development of improved live recombinant viral vectors and better animal models for AIDS vaccines. Vectors include adeno-associated virus, non-replicating pox-viruses and replication pox-viruses that lack factors involved in evading the host immune response. A scid mouse model will be improved to enhance engraftment and allow induction of primary immune responses. 5. Design and manufacture of new candidate AIDS vaccines for clinical trials in humans. Second-generation vaccines will be generated immediately, based on current knowledge. Third-generation vaccines will be designed after accumulating additional information on correlates of immunity, optimal antigen conformation, combinations with immunomodulatory molecules, and viral vector improvements.

该计划的长期目标是开发有效的 使用新型重组病毒载体的艾滋病毒疫苗。朝这个方向 最后，该提案的目标是更好地理解 针对 HIV 的保护性免疫反应并设计新抗原 配置和改进的载体来引发这些保​​护性免疫 回应。该计划的合并项目有五个主要具体内容 目标： 1. 个体对 HIV 免疫反应的比较 表现出长期非进行性艾滋病毒感染 HIV 感染的正常进展。 2. 修饰HIV和SIV基因以增强抗原呈递， 将这些改变的基因插入痘病毒载体，并评估 这些重组病毒在啮齿动物体内。此类修改旨在 增加蛋白质加工，增强或改变细胞内的方向 运输，或暴露隔离的表位。共刺激分子将 包括在内以增强细胞免疫反应。 3.编码中和HIV的有效抗体的基因的表达。基因 编码广泛中和抗体将被插入重组 腺相关病毒可提供高水平的中和抗体 到流通。 4. 改进活重组病毒载体的开发和更好的 艾滋病疫苗的动物模型。载体包括腺相关病毒、 非复制型痘病毒和缺乏因子的复制型痘病毒 参与逃避宿主免疫反应。 scid 小鼠模型将是 改进以增强植入并允许诱导初级免疫 回应。 5. 临床艾滋病候选疫苗的设计与生产 人体试验。第二代疫苗将产生 立即，根据现有知识。第三代疫苗将 在积累了有关相关因素的附加信息后设计的 免疫、最佳抗原构象、与免疫调节剂的组合 分子和病毒载体的改进。