HSV Amplicon Vectors for HIV Vaccine Development

用于 HIV 疫苗开发的 HSV 扩增子载体

• 批准号: 6408835
• 负责人: Thomas G Evans
• 金额: $ 22.07万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6408835
• 关键词: Herpesviridae vaccine; MHC class I antigen; MHC class II antigen; antigen antibody reaction; biotechnology; cell line; cell mediated lymphocytolysis test; cellular immunity; cytotoxic T lymphocyte; drug delivery systems; drug design /synthesis /production; drug screening /evaluation; enzyme linked immunosorbent assay; gene expression; genetic mapping; genetically modified animals; helper T lymphocyte; herpes simplex virus 1; human immunodeficiency virus 1; humoral immunity; laboratory mouse; neutralizing antibody; transfection /expression vector; vaccine development; vector vaccine; western blottings

DESCRIPTION: (Provided by Applicant) The development of an effective prophylactic vaccine for HIV-1 will likely need an immunogen that can induce neutralizing antibody, and CD4 and CD8 T cell activity. Viral vector systems that infect cells and allow intracellular expression of HIV-1 gene products have the ability to activate T cells through MHC class I and II presentation. Herpes simplex virus type-1 (HSV-1) amplicons possess many of the desirable features of such a viral vector system. They are non-replicating, induce robust CD8+ T cell responses in mice, are easily manufactured, and infect a variety of antigen presenting cells, including dendritic cells. The HSV-1 amplicon can incorporate large segments of DNA, express more than one gene product, are not contaminated by helper virus, and are under development and evaluation as gene therapy tools. In initial experiments, HSV-1 amplicons expressing HIV-1 MN gp120 were shown capable of inducing interferon gamma-producing T cells at a number equivalent to that induced by live herpesvirus vectors, and far exceeding that of a modified vaccinia Ankara vector. In addition, the amplicons induced large anti-Env antibody responses. Building upon these observations, three specific aims are proposed. The first will be to construct amplicons which express codonoptimized clade C env, gag, and tat genes, and evaluate the protein expression from such vectors in vitro. In the second aim, the optimum route of parenteral and mucosal delivery, the dose and duration of immunity, and the effect of prior immunity to HSV will be evaluated. Lastly, the immune responses induced by the clade C amplicon will be evaluated in BALB/c and mapped in HLA-A2/human beta2 microglobulin transgenic mice. Overall, it is anticipated that these experiments will generate sufficient data to warrant moving the HSV-1 amplicon vaccine concept into non-human primate and human vaccine trials.

描述：（由申请人提供）开发有效的HIV-1预防性疫苗可能需要一种可以诱导的免疫原