Nasal SIV vaccination in female macaques/AIDS prevention

雌性猕猴鼻 SIV 疫苗接种/艾滋病预防

• 批准号: 7017037
• 负责人: ANNA ALDOVINI
• 金额: $ 62.48万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-15 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7017037
• 关键词: AIDS education /prevention; AIDS therapy; AIDS vaccines; Adenoviridae; HIV infections; Macaca mulatta; active immunization; biotechnology; colony stimulating factor; female; helper T lymphocyte; humoral immunity; immune response; immunoglobulin A; immunomodulators; inhalation drug administration; interleukin 12; interleukin 15; interleukin 2; lymphocyte proliferation; mucosal immunity; nonhuman therapy evaluation; simian immunodeficiency virus; tumor necrosis factor alpha; vaccine development; vaccine evaluation; vector vaccine

DESCRIPTION (provided by applicant): More than 80% of global transmission of HIV infection occurs via mucosal routes. The ability of vaccines to induce mucosal immunity may be required for protection against HIV infection and the immunodeficiency syndrome that emerges after infection. Various AIDS vaccine candidates are currently under development, each with potential advantages and disadvantages. DNA vaccines have features that make them attractive vaccine candidates for HIV and the combination of DNA vaccination plus recombinant vaccinia is one of the favored approaches in AIDS vaccine development. We have established a vaccination regimen via the nasal route that stimulates mucosal and systemic responses with a SHIV DNA vaccine, which consists of a single plasmid carrying a SHIV proviral genome that produces noninfectious particles. We have the appropriate tools to measure SHIV- and SlV-specific IgA levels in mucosal secretions, mucosal cell-mediated responses, and SHIV and SlV-specific humoral and cellular systemic responses. As a consequence, we believe that we are well placed to establish the effectiveness of mucosal vaccination and how stimulation of virus-specific mucosal and systemic responses may affect the efficacy of a HIV/SIV vaccine. This proposal is designed to extend on going studies by investigating approaches restricted to the nasal route and evaluate their efficacy in female animals. Towards this goal we propose: 1) to evaluate whether the addition of different cytokines to the DNA priming portion of the SIV DNA-MVA regimen leads to both systemic and mucosal virus specific immune responses that are different in magnitude or in mucosal/systemic ratio than those observed with SHIV-IL-2/Ig; 2) to compare which of two immunization regimens (SIV+ cytokines DNA priming followed by boosting with 1. recombinant adenovirus or 2. genitically inactivated SIV particles) administered via the nasal route better engenders high levels of both mucosal and systemic immune responses in female macaques that can provide significant control of viremia and disease progression. The results of this investigation may have important implications for AIDS vaccine development and for the development of DNA vaccines for other mucosal pathogens.

描述（由申请人提供）：超过80％的全球艾滋病毒感染传播是通过粘膜路线发生的。疫苗诱导粘膜免疫的能力可能需要防止HIV感染和感染后出现的免疫缺陷综合症。各种艾滋病疫苗候选者目前正在开发中，每种疫苗都有潜在的优势和缺点。 DNA疫苗的特征使其具有吸引力的HIV疫苗，而DNA疫苗接种加重组疫苗的组合是AIDS疫苗开发中最受欢迎的方法之一。 我们已经通过鼻腔途径建立了一种疫苗接种方案，该方案用SHIV DNA疫苗刺激粘膜和全身反应，该疫苗由带有SHIV病毒基因组的单个质粒组成，该基因组产生非感染性颗粒。我们有适当的工具来测量粘膜分泌，粘膜细胞介导的反应以及SHIV和SLV特异性的体液和细胞全身反应中的SHIV和SLV特异性IgA水平。因此，我们认为我们有足够的位置来确定粘膜疫苗接种的有效性，以及病毒特异性粘膜和全身反应的刺激如何影响HIV/SIV疫苗的功效。 该建议旨在通过调查局限于鼻途径的方法来扩展进行研究，并评估其在雌性动物中的功效。为了实现这一目标，我们建议：1）评估在SIV DNA-MVA方案的DNA启动部分中添加不同的细胞因子是否会导致全身性和粘膜病毒特异性免疫反应在大小上或粘膜/全身性比率不同于Shiv-il-il-2/Ig; 2）比较两种免疫方案中的哪种（SIV+细胞因子DNA启动，然后增强1（重组腺病毒）或2个。通过鼻途径通过鼻途径施用的恒生灭活的SIV颗粒）可以更好地产生女性乳腺癌的粘膜和全身性免疫应对，从而可以提供严重的疾病和疾病的疾病。这项研究的结果可能对艾滋病疫苗的开发以及其他粘膜病原体的DNA疫苗开发具有重要意义。