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
- 来源:
- 关键词:2019-nCoVAN-1792Administrative SupplementAgeAge-YearsAlzheimer&aposs disease modelAmyloid beta-42Amyloid beta-ProteinAntibodiesAntibody titer measurementAntiviral AgentsB-Lymphocyte EpitopesB-LymphocytesBiological AssayCD8-Positive T-LymphocytesCOVID-19COVID-19 pandemicCell Culture TechniquesCellsCessation of lifeCoronavirusCritical IllnessDNADNA VaccinesDataDeath RateDevelopmentDisease OutbreaksEbola virusElderlyEngineeringEpitopesFutureGene ProteinsGenerationsGenesGeneticGenetic PolymorphismGlycoproteinsGoalsGrantHumanHumoral ImmunitiesImmune SeraImmune responseImmunizationImmunizeImmunocompromised HostImmunoglobulin GIndividualInfectionInfluenzaInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H5N1 SubtypeInterferon Type IIInterleukin-10Interleukin-6LeadLongevityLungLymphopeniaMacaca fascicularisMemoryMeningoencephalitisMiddle East Respiratory SyndromeMiddle East Respiratory Syndrome CoronavirusModelingMonkeysMusNucleic AcidsPathologicPatientsPeptidesPlasmaPlayProductionProteinsQS21Recombinant VaccinesReportingRestRoleSARS coronavirusSafetySeriesSerious Adverse EventSeverity of illnessSplenocyteSuggestionT cell responseT memory cellT-Cell ActivationT-LymphocyteT-Lymphocyte EpitopesTNF geneTauopathiesTechnologyTestingTimeTransgenic MiceTransgenic OrganismsVaccinatedVaccinationVaccine DesignVaccinesViralViral VaccinesVirusVirus DiseasesVulnerable Populationsadaptive immunityagedalpha synucleinautoreactive T cellbasecytokinecytokine release syndromedesignefficacy testingimmunogenicimmunogenicityimmunopathologyimmunosenescencemortalitymouse modelneutralizing antibodynonhuman primatenovel coronaviruspathogenphase I trialpreventprogramsprototyperesponsetau Proteinsvaccine evaluation
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).
项目概要
在美国首次报告因 COVID-19 死亡的两个月后,死亡率为每百万人 228 人,
全球第十高的比率。 45-54 岁人群中 COVID-19 死亡率约为 5%,并且还在上升
50-60 岁人群中的死亡率高达 13%,遗憾的是,美国所有冠状病毒死亡病例中有 80% 发生在 65 岁人群中
岁及以上。为了保护人们免受 COVID-19 的侵害,世界各地的多个团体已经开始
开发基于 SARS-CoV-2 基因序列的疫苗。我们不知道蜂窝和
体液免疫反应对于预防 SARS-CoV-2 是必要的,但最近的数据
对 COVID-19 患者进行恢复期血浆注射表明疫苗可诱导中和
抗体足以预防这种感染。更重要的是,疫苗有可能
含有目前未知的 SARS-CoV-2 T 细胞表位,可能会在免疫受试者中诱导细胞因子
随后的病毒感染风暴可能会导致严重的不良事件,最终导致死亡
尤其是老年人易受影响。为了避免自身反应性 T 细胞激活,使用当前的 AG060965
计划和其他 NIA 拨款,我们开发了一种通用且极具免疫原性的 MultiTEP 疫苗
针对病理性 Aβ、tau 和 α-Syn 的 A.D. 疫苗平台。利用这一发展优势,我们
在本行政补充文件中提议创建基于专有 MultiTEP 的 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)中存在抗体。这种疫苗可能与许多疫苗不同
其他原因是它可以刺激适应性免疫,提供人类 MHC 多态性的广泛覆盖
并激活幼稚 Th 细胞和响应传统方法而产生的预先存在的记忆 Th 细胞
在一个人的一生中接种疫苗和/或感染各种病原体,但没有激活有害病毒-
特异性T细胞。因此,利用我们基于核酸的疫苗技术,我们将快速生成DNA
通过将刺突蛋白中的 20 个 B 细胞表位基因连接到 MultiTEP 来构建,(ii) 选择几个 B 细胞
在小鼠体内诱导病毒中和抗体的表位,(iii) 生成原型重组疫苗 CoV2-
2019 同时靶向多达三个与中和抗体产生相关的 B 细胞表位。
这种多表位 CoV2-2019 疫苗将在老年非人类灵长类动物(年龄相关模型)中进行测试
免疫衰老)AD/tau蛋白病转基因小鼠模型(老年人疫苗接种的季节性模型)
人和 MCI/AD 患者之前接种过 tau 疫苗,AV-1980)。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(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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