Combination DNA and Attenuated Virus Vaccine for SIV

描述：（改编自申请人摘要）疫苗的开发 艾滋病毒/艾滋病是一个紧迫的优先事项。每年都有数百万新的艾滋病毒感染者 这些感染率在发展中国家正在增加， 国家这些地区无法获得抗逆转录病毒治疗，因此， 希望是研制出安全有效的疫苗。最有用的模型 是SIV感染的猕猴。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 由于使用不同的SIV分离株， 致病性已经测试过的最有效的疫苗是 基因缺失的减毒活SIV（SIV delta nef及其衍生物）。然而，在这方面， 这些疫苗的有效性由于安全性问题（疾病 接种病毒的新生儿的发育），以及 接种疫苗，以达到最大的保护效果。DNA免疫 最近被证明可以有效地引发对艾滋病毒和SIV的免疫反应 抗原然而，DNA本身不能诱导保护，需要加强， 如表达SIV抗原的重组痘病毒。不过，目前尚不清楚， 这种方法将提供长期保护。由于有效的 减毒活病毒在产生保护性免疫方面的作用， 基于DNA的技术诱导的强启动，我们假设， 这两种疫苗系统的组合可以提供优异的组合疫苗。 免疫缺陷病毒疫苗接种方案。为了验证这一 假设，我们建议比较免疫原性（在猕猴）的DNA 免疫接种，然后进行减毒活疫苗加强接种，即活疫苗加强接种 单独施用减毒病毒。体液和细胞免疫应答 将被充分表征，如将在活减毒后的病毒参数 病毒增强。然后用致病性SHIV89.6p攻击动物 活的减毒病毒给药后。动物们将在 评价了对感染的保护和对病原体的保护 影响（CD 4 + T细胞下降，高病毒载量）。这些研究将使 DNA/减毒活病毒联合免疫 策略和单独减毒活疫苗策略。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， 耶基斯中心

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.