Adjuvant combination for SARS-CoV-2 vaccine for the elderly

老年人SARS-CoV-2疫苗的佐剂组合

• 批准号: 10662196
• 负责人: Elena Vassilieva
• 金额: $ 19.56万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-08 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10662196
• 关键词: 2019-nCoV; Address; Adjuvant; Adult; Affect; Age Years; Agonist; Animals; Antigens; Authorization documentation; COVID-19 vaccine; Cells; Cessation of life; Clinical Research; Combined Vaccines; Cytotoxic T-Lymphocytes; Data; Development; Disease; Dose; Elderly; Emergency Situation; Formulation; Immune response; Immunity; Individual; Influenza; Interferons; Licensing; MF59; Mus; Outcome; Pathway interactions; Persons; Production; Proteins; Quil A; RNA vaccine; Recombinant Proteins; Research; Safety; Saponins; Stimulator of Interferon Genes; Subunit Vaccines; Testing; Translations; Universities; Vaccinated; Vaccination; Vaccine Antigen; Vaccines; aged; aging population; authority; coronavirus disease; cytokine; experience; high risk; immunogenicity; immunosenescence; improved; influenza virus vaccine; middle age; mouse model; neutralizing antibody; novel; older patient; pandemic disease; response; sex; vaccine candidate; vaccine development; vaccine response; young adult

PROJECT SUMMARY Severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is currently causing the coronavirus disease (COVID-19) in pandemic proportion. According to John Hopkins university data tracker, there were 120,217,175 global cases and 2,660,456 deaths worldwide on March 15, 2021. The disease ranges from asymptomatic to lethal, with the elderly patients most severely affected. Finding a successful strategy to protect most vulnerable aged population is vital. However, it is possible that protein-based vaccines will not be as effective in individuals over 65 years of age as in healthy younger adults. There are also indications that RNA vaccines that are currently used under emergency authorization elicit vaccine responses appear weaker in elderly . Protein-based vaccines are considered safe but they lack the ability to elicit Th1 type of responses especially needed for protection in aged populations. Recently we developed a novel combination adjuvant for use with a licensed influenza subunit vaccine in high-risk aged population and tested it in an aged mouse model. The formulation combines an agonist of the stimulator of interferon gene (STING) pathway 2,3’-cGAMP and saponin Quil-A. Activation of the STING pathway leads to production of interferons and cytokines in target cells, and enhances development of the immune response to vaccine antigens, while saponins stimulate both the Th1 immune response and cytotoxic T lymphocyte production against protein antigens. By co-delivering these two compounds, cGAMP and Quil-A, with the vaccine we combined their adjuvant potential and improved the protective immunity of influenza vaccine in the aged mice more effectively than either a 4x antigen dose or MF-59-like adjuvant, which are two current vaccination options for persons over 65 years of age. We propose that this combination will also potentiate the protective responses to a candidate SARS-CoV-2 vaccine and will test this in aged mice. We will test this hypothesis using both sexes of aged mice. As saponins have been previously shown to increase the duration of immune response we will also determine the persistence of neutralizing antibodies in vaccinated animals. Although we do not anticipate reactogenicity of this formulation based on our experience, we will also test if a novel and safer saponin Titerquil 1-0-5-5 can be used instead of Quil-A. The results will be directly relevant for development of SARS-CoV-2 protein vaccines for high-risk aged populations. The combination adjuvant can be directly added to existing vaccines.

项目摘要 严重的急性呼吸道综合征-Coronavirus 2（SARS-COV-2）目前正在引起 大流行比例的冠状病毒病（Covid-19）。根据约翰·霍普金斯大学的说法 数据跟踪器，那里 3月15日，全球120,217,175例全球案件和2,660,456例死亡 2021。 该疾病的范围从不对称到致命，老年患者最严重 做作的。寻找一种成功的策略来保护大多数脆弱的老年人口至关重要。 但是，基于蛋白质的疫苗在65岁以上的个体中可能不会有效 年龄与健康的年轻人一样。 也有迹象表明RNA疫苗是 目前在紧急授权下使用的引起疫苗反应在较早的情况下似乎较弱 。 基于蛋白质的疫苗被认为是安全的，但缺乏引起Th1类型反应的能力 特别是在老年人群中保护所需的。最近我们开发了一种新颖的组合 调整可与有执照的Hypisten人群中的有执照的影响力亚基疫苗一起使用并进行了测试 它在老年鼠标模型中。该公式结合了干扰素刺激器的激动剂 基因（Sting）途径2,3'-cgamp和皂苷Quil-a。激活刺激途径引线 在靶细胞中生产干扰素和细胞因子，并增强 对疫苗抗原的免疫反应，而皂苷刺激了Th1免疫反应 与蛋白质抗原的细胞毒性T淋巴细胞产生。通过共同交付这两个 化合物，CGAMP和Quil-A，与疫苗一起，我们将其可调节电位结合在一起 比相比 4倍抗原剂量或类似MF-59的调节，这是两个当前的疫苗接种选择 超过65岁的人。我们建议这种组合也可能受到保护 对候选SARS-COV-2疫苗的反应，并将在老年小鼠中进行测试。我们将测试这个 使用老年小鼠的两性假设。因为先前已显示皂苷会增加 免疫反应的持续时间我们还将确定中和的持久性 接种动物的抗体。尽管我们没有预期这种公式的反应生成性 根据我们的经验，我们还将测试一个小说，更安全的皂苷titerquil 1-0-5-5 代替quil-a。结果将与SARS-COV-2的开发直接相关 高危老年人群的蛋白质疫苗。可以直接添加组合调整 到现有疫苗。