Combination DNA and Attenuated Virus Vaccine for SIV

用于 SIV 的 DNA 和减毒病毒组合疫苗

• 批准号: 6348396
• 负责人: FRANCIS J NOVEMBRE
• 金额: $ 32万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6348396
• 关键词: AIDS vaccines; Macaca; T lymphocyte; active immunization; attenuated microorganism; cellular immunity; humoral immunity; live vaccine; simian immunodeficiency virus; vaccine development; vector vaccine; virus load

DESCRIPTION: (Adapted from Applicant's Abstract) The development of a vaccine for HIV/AIDS is an urgent priority. Millions of new HIV infections occur each year, and the rate of these infections is on the increase in developing countries. These areas have no access to antiretroviral therapy, so the only hope is development of a safe and efficacious vaccine. The most useful model for vaccine development has been the SIV-infected macaque. While a number of vaccine strategies have been tested in this model system, results are often complicated by the use of different isolates of SIV, which vary in their pathogenicity. The most efficacious vaccines that have been tested are the gene-deleted live attenuated SIVs (SIV delta nef and its derivatives). However, the effectiveness of these vaccines are complicated by safety issues (disease development in neonates vaccinated with virus), and the delay, following vaccination, to reach the maximum protective effect. DNA-based immunizations have recently been shown to effectively prime immune responses to HIV and SIV antigens. However, DNA alone cannot induce protection and requires a boost, such as a recombinant poxvirus expressing SIV antigens. Still, it is unknown if this methodology will afford long-term protection. Because of the efficacy of live attenuated viruses at generating protective immunity and because of the strong priming induced by DNA-based technologies, we hypothesize that a combination of these two vaccine systems may provide an excellent combined regimen for vaccination against immunodeficiency viruses. To test this hypothesis, we propose to compare the immunogenicity (in macaques) of a DNA immunization followed by a live attenuated boost, with that of a live attenuated virus administration alone. Humoral and cellular immune responses will be fully characterized, as will viral parameters following live attenuated virus boost. Animals will then be challenged with the pathogenic SHIV89.6p following live attenuated virus administration. Challenged animals will be evaluated for protection from infection and for protection from pathogenic effects (CD4+ T cell decline, high viral loads). These studies will allow a comparison between a combination DNA/live attenuated virus immunization strategy and a live attenuated alone strategy. Additionally, these studies will allow a comparison to other DNA-based strategies currently being utilized at the Yerkes Center.

描述：（改编自申请人的摘要）疫苗的开发 防治艾滋病毒/艾滋病是当务之急。每年新增数百万艾滋病毒感染者 年，这些感染率在发展中国家呈上升趋势 国家。这些地区无法获得抗逆转录病毒治疗，因此唯一的方法是 希望是开发出安全有效的疫苗。最有用的模型 感染 SIV 的猕猴一直是疫苗开发的主要对象。虽然一些 疫苗策略已在该模型系统中进行了测试，结果通常是 由于使用不同的 SIV 分离株而使情况变得复杂，这些分离株的特性各不相同 致病性。经测试最有效的疫苗是 基因删除的减毒活 SIV（SIV delta nef 及其衍生物）。然而， 这些疫苗的有效性因安全问题（疾病 接种病毒的新生儿的发育），以及延迟，如下 接种疫苗，以达到最大的保护效果。基于 DNA 的免疫接种 最近被证明可以有效地启动针对 HIV 和 SIV 的免疫反应 抗原。然而，DNA 本身无法产生保护作用，需要加强， 例如表达SIV抗原的重组痘病毒。尽管如此，尚不清楚是否 这种方法将提供长期保护。因为功效 减毒活病毒可产生保护性免疫力，并且由于 基于 DNA 的技术诱导的强启动，我们假设 这两种疫苗系统的结合可能会提供极好的组合 免疫缺陷病毒疫苗接种方案。为了测试这个 假设，我们建议比较 DNA 的免疫原性（在猕猴中） 免疫接种后进行减毒活疫苗加强免疫 单独施用减毒病毒。体液和细胞免疫反应 将得到充分表征，减毒活病毒参数也将得到充分表征 病毒增强。然后动物将受到致病性 SHIV89.6p 的攻击 施用减毒活病毒后。受到挑战的动物将 评估了对感染的保护和对病原体的保护 效应（CD4+ T 细胞下降、高病毒载量）。这些研究将允许 DNA/减毒活病毒组合免疫之间的比较 策略和活衰减单独策略。此外，这些研究将 允许与目前正在使用的其他基于 DNA 的策略进行比较 耶克斯中心。