Repurposing of Universal and Immunogenic MultiTEP Platform Designed for AD to Develop SARS-CoV-2 Multiepitope Vaccine

重新利用专为 AD 设计的通用和免疫原性 MultiTEP 平台来开发 SARS-CoV-2 多表位疫苗

基本信息

  • 批准号:
    10162389
  • 负责人:
  • 金额:
    $ 38.91万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-02-01 至 2022-01-31
  • 项目状态:
    已结题

项目摘要

Project Summary Two months after the first report of a U.S. death from COVID-19, the death rate is 228 per million people, the tenth highest rate globally. The mortality rate from COVID-19 in those aged 45-54 years is ~5%, and it increased to 13% in people of 50-60 years old, and sadly 80% of all U.S. coronavirus deaths occurred among people 65 years of age and older. To protect people from COVID-19, multiple groups in all over the world have begun developing vaccines based on the genetic sequence of SARS-CoV-2. We do not know whether both cellular and humoral immune responses are necessary for protection against the SARS-CoV-2, but recent data with convalescent plasma administration into the COVID-19 patients indicate that vaccine inducing neutralizing antibodies could be sufficient for the protection against this infection. More of that, it is possible that a vaccine that contains currently unknown T cell epitopes of SARS-CoV-2 may induce in immunized subjects a cytokine storm upon subsequent viral infection that could lead to severe adverse events, culminating in death in particularly susceptible elderly individuals. To avoid autoreactive T cell activation, using the current AG060965 program and other NIA grants, we have developed a universal and extremely immunogenic MultiTEP vaccine platform for A.D. vaccines targeting pathological Aβ, tau, and α-Syn. Taking advantage of this development we propose in this Administrative Supplement to create a SARS-CoV-2 vaccine based on proprietary MultiTEP platform technology. We hypothesize that MultiTEP platform-based vaccine could induce protective neutralizing antibodies in immunocompromised elderly people, including MCI/AD patients. This vaccine may differ from many others because it could stimulate adaptive immunity, providing broad coverage of human MHC polymorphisms and activating both naive Th cells and pre-existing memory Th cells generated in response to conventional vaccines and/or infections with various pathogens during one's lifespan without the activation of harmful virus- specific T cells. Therefore, using our nucleic acid-based vaccine technology we will rapidly generate DNA constructs by attaching twenty B cell epitope genes from the spike protein to MultiTEP, (ii) select several B cell epitopes that induced virus-neutralizing antibodies in mice, (iii) generate prototype recombinant vaccine, CoV2- 2019 targeting simultaneously up to three B cell epitopes associated with production of neutralizing antibodies. This multiepitope CoV2-2019 vaccine will be tested in aged non-human primates (model of age-associated immunosenescence) ana transgenic mouse model of A.D./tauopathy (seasonal model of vaccination of elderly people and MCI/AD patients previously vaccinated with tau-vaccine, AV-1980).
项目摘要 在美国首次报告COVID-19死亡两个月后,死亡率为每百万人228人, 全球排名第十。45-54岁人群的COVID-19死亡率约为5%, 在50-60岁的人群中,这一比例为13%,可悲的是,美国80%的冠状病毒死亡病例发生在65岁以上的人群中。 年龄和年龄更大。为了保护人们免受COVID-19的影响,世界各地的多个团体已经开始 根据SARS-CoV-2的基因序列研制疫苗。我们不知道细胞和 体液免疫应答对于预防SARS-CoV-2是必要的,但最近的数据显示, 对COVID-19患者的恢复期血浆给药表明,疫苗诱导中和 抗体可能足以防止这种感染。更重要的是,疫苗有可能 含有目前未知的SARS-CoV-2的T细胞表位的疫苗可以在免疫受试者中诱导细胞因子 随后的病毒感染可能导致严重的不良事件,最终导致死亡, 尤其是老年人。为了避免自身反应性T细胞活化,使用当前AG 060965 计划和其他NIA赠款,我们已经开发了一种通用的和极免疫原性的MultiTEP疫苗 靶向病理性Aβ、tau和α-Syn的AD疫苗平台。利用这一发展,我们 在本行政补充文件中,我建议根据专利MultiTEP创建SARS-CoV-2疫苗 平台技术我们假设基于MultiTEP平台的疫苗可以诱导保护性中和, 免疫功能低下的老年人,包括MCI/AD患者的抗体。这种疫苗可能不同于许多 另一些是因为它可以刺激适应性免疫,提供了人类MHC多态性的广泛覆盖 以及激活初始Th细胞和预先存在的记忆Th细胞两者,所述记忆Th细胞响应于常规免疫应答而产生。 疫苗和/或在人的一生中感染各种病原体,而不会激活有害病毒- 特异性T细胞因此,利用我们的核酸疫苗技术, 通过将来自刺突蛋白的20个B细胞表位基因连接到MultiTEP构建体,(ii)选择几个B细胞表位基因, 在小鼠中诱导病毒中和抗体的表位,(iii)产生原型重组疫苗,CoV 2- 2019同时靶向与中和抗体产生相关的多达三个B细胞表位。 这种多表位CoV 2 -2019疫苗将在老年非人灵长类动物中进行测试(与年龄相关的模型)。 A.D./A.D.转基因小鼠模型tau病(老年人疫苗接种的季节性模型 人和先前用tau疫苗AV-1980接种的MCI/AD患者)。

项目成果

期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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Michael G Agadjanyan其他文献

Expression of the Epigenetic factor BORIS (CTCFL) in the Human Genome
  • DOI:
    10.1186/1479-5876-9-213
  • 发表时间:
    2011-12-01
  • 期刊:
  • 影响因子:
    7.500
  • 作者:
    Rosalia de Necochea-Campion;Anahit Ghochikyan;Steven F Josephs;Shelly Zacharias;Erik Woods;Feridoun Karimi-Busheri;Doru T Alexandrescu;Chien-Shing Chen;Michael G Agadjanyan;Ewa Carrier
  • 通讯作者:
    Ewa Carrier

Michael G Agadjanyan的其他文献

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{{ truncateString('Michael G Agadjanyan', 18)}}的其他基金

Manufacturing of New Batch AV-1959D Drug Product and Placebo for Phase 1 Trial
为 1 期试验生产新批次 AV-1959D 药品和安慰剂
  • 批准号:
    10732215
  • 财政年份:
    2022
  • 资助金额:
    $ 38.91万
  • 项目类别:
Safety/Tolerability/Immunogenicity of first-in-human Aβ DNA vaccine, AV-1959D Phase 1 trials in early-stage AD subjects: based on IND18953 cleared by FDA.
首个人类 Aβ DNA 疫苗的安全性/耐受性/免疫原性,AV-1959D 在早期 AD 受试者中的 1 期试验:基于 FDA 批准的 IND18953。
  • 批准号:
    10340654
  • 财政年份:
    2022
  • 资助金额:
    $ 38.91万
  • 项目类别:
Safety/Tolerability/Immunogenicity of first-in-human Aβ DNA vaccine, AV-1959D Phase 1 trials in early-stage AD subjects: based on IND18953 cleared by FDA.
首个人类 Aβ DNA 疫苗的安全性/耐受性/免疫原性,AV-1959D 在早期 AD 受试者中的 1 期试验:基于 FDA 批准的 IND18953。
  • 批准号:
    10571883
  • 财政年份:
    2022
  • 资助金额:
    $ 38.91万
  • 项目类别:
Manufacturing of Drug Product, Dual Aβ/tau Vaccine for Clinical Trials
药品生产,用于临床试验的双重 Aβ/tau 疫苗
  • 批准号:
    10667237
  • 财政年份:
    2019
  • 资助金额:
    $ 38.91万
  • 项目类别:
Evaluation of Safe and Immunogenic Dose of AD Vaccine in aged non-human primates: Prelude to Phase 1 Preventive Vaccinations
AD 疫苗在老年非人灵长类动物中的安全和免疫原性剂量评估:第一阶段预防性疫苗接种的前奏
  • 批准号:
    10433497
  • 财政年份:
    2019
  • 资助金额:
    $ 38.91万
  • 项目类别:
Cooperative program U01 AG060965 Supplement: "Preparation of IND for Dual Aβ/Tau AD Vaccine for submission to FDA"
合作计划 U01 AG060965 补充:“双 Aβ/Tau AD 疫苗 IND 的准备以提交给 FDA”
  • 批准号:
    10505652
  • 财政年份:
    2019
  • 资助金额:
    $ 38.91万
  • 项目类别:
IND-enabling Preclinical Studies on Anti-Tau AD Vaccine for Phase 1 Trial
抗 Tau AD 疫苗 1 期试验的 IND 临床前研究
  • 批准号:
    10364623
  • 财政年份:
    2019
  • 资助金额:
    $ 38.91万
  • 项目类别:
Combining AD Epitope Vaccine with Innate Immunity
AD表位疫苗与先天免疫相结合
  • 批准号:
    9439835
  • 财政年份:
    2017
  • 资助金额:
    $ 38.91万
  • 项目类别:
Pre-clinical study to fulfill FDA requirements for the completion of AV-1959 IND
临床前研究以满足 FDA 完成 AV-1959 IND 的要求
  • 批准号:
    8887223
  • 财政年份:
    2015
  • 资助金额:
    $ 38.91万
  • 项目类别:
Pre-clinical study to fulfill FDA requirements for the completion of AV-1959 IND
临床前研究以满足 FDA 完成 AV-1959 IND 的要求
  • 批准号:
    9264954
  • 财政年份:
    2015
  • 资助金额:
    $ 38.91万
  • 项目类别:
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