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
基本信息
- 批准号:10433497
- 负责人:
- 金额:$ 41.95万
- 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 2023-01-31
- 项目状态:已结题
- 来源:
- 关键词:Active ImmunotherapyAdjuvantAdministrative SupplementAducanumabAlzheimer disease preventionAlzheimer&aposs disease modelAlzheimer&aposs disease related dementiaAmyloidAmyloid beta-42Amyloid beta-ProteinAntibodiesAntibody titer measurementB-Lymphocyte EpitopesB-LymphocytesBehavioralBiochemistryBiological AssayBiological MarkersBiological ProcessBloodBrainC-reactive proteinClinicalClinical DataClinical TrialsCombined Modality TherapyCyclic GMPDataDiseaseDisease ProgressionDisease modelDoseEarly InterventionEarly treatmentEmergency SituationEnzyme-Linked Immunosorbent AssayEvaluationFemaleFutureGenetic PolymorphismGoalsHelper-Inducer T-LymphocyteHumanImmune systemImmunizationImmunizeImmunotherapeutic agentImmunotherapyIn VitroInfectionInflammationInjectionsInterferon Type IIIntramuscularLongevityMacaca fascicularisMemoryMethodsMonitorMonkeysMonoclonal AntibodiesMusOnset of illnessPaperPassive ImmunotherapyPathologicPathologic ProcessesPathologyPeripheral Blood Mononuclear CellPhasePreventative vaccinationPreventivePreventive treatmentProductionPublishingRecombinant ProteinsReportingResearchRiskSafetySiteTestingTherapeuticTimeTimeLineToxic effectToxicologyVaccine Clinical TrialVaccinesadaptive immunityage groupagedautoreactive T cellautoreactivitybasefirst-in-humanimmunogenicimmunogenicitymalemeetingsmouse modelmultidisciplinarymultiple omicsnon-dementednonhuman primatenovelpathogenphase I trialpre-clinicalpreventprogramsresponsesynergismtargeted treatmenttau Proteinstau aggregationtau-1therapy developmenttreatment strategyvaccine developmentvaccine trial
项目摘要
Project Summary
Immunotherapy is still considered a very promising therapeutic strategy for AD prevention when
certain conditions are met. Data from various immunotherapeutic studies support our long-
standing tenet that immunogenic AD vaccines could at least delay disease progression when they
target both Aβ and Tau pathological molecules at an early stage of the disease before AD
manifestation or even in asymptomatic healthy people at risk of AD. Recently FDA announced
emergency accelerated approval of mAb Aducanumab for treatment of early AD. However, it is
impractical to use very expensive mAbs as a preventive treatment of healthy subjects due to the
need for frequent (monthly) administration of high concentrations (700-800mg per IV injection) of
this immunotherapeutic. In contrast, almost all effective vaccines are effective when they are used
as a preventive treatment. Accordingly, in this administrative supplement to U01 AG060965, we
propose to test the overall safety and immunogenicity of a dual vaccine (DUVAC) targeting Aβ
and Tau in non-human primates that more closely resemble the human immune system. These
data will support the submission of INDs to the FDA for future clinical trials that will allow us to
treat asymptomatic healthy subjects at risk to MCI with extremely immunogenic Aβ and tau
vaccines based on the same and very immunogenic MultiTEP platform and novel adjuvant
AdvaxCpG. Our proprietary vaccine platform can 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 autoreactive T cells. These
"non-self" Th cells should activate B cells and induce the production of therapeutically potent
antibodies specific to pathological Aβ and Tau in humans, similar to that in non-human primates.
Completing studies in aged monkeys along with data from AG060965 safety/toxicology studies in
diseased mice should strongly support our IND submission for the first-in-human preventive dual
Aβ/tau vaccine with healthy people at risk of MCI or earlier based on research blood, CSF, brain
biomarkers.
项目摘要
免疫疗法仍然被认为是预防阿尔茨海默病的一种非常有前途的治疗策略
满足某些条件。来自各种免疫治疗研究的数据支持我们的长期-
坚持的原则是,免疫原性AD疫苗至少可以延缓疾病的进展,当它们
在AD之前的疾病早期阶段同时靶向Aβ和Tau病理分子
甚至在无症状的健康人群中表现为阿尔茨海默病。FDA最近宣布
紧急加速批准单抗Aducanumab用于治疗早期AD。然而,它是
使用非常昂贵的单抗作为健康受试者的预防性治疗是不切实际的,因为
需要经常(每月)服用高浓度(每次静脉注射700-800毫克)
这种免疫疗法。相比之下,几乎所有有效的疫苗在使用时都是有效的
作为一种预防性治疗。因此,在U01 AG060965的这一行政副刊中,我们
建议测试针对β的双重疫苗的整体安全性和免疫原性
和Tau在非人类灵长类动物中更接近于人类的免疫系统。这些
数据将支持将IND提交给FDA进行未来的临床试验,这将使我们能够
用极具免疫原性的A、β和tau治疗有轻度脑梗塞风险的无症状健康患者
基于同一高度免疫原性多TEP平台和新型佐剂的疫苗
AdvaxCpG。我们的专有疫苗平台可以刺激适应性免疫,提供广泛的
人类MHC基因多态及激活初始Th细胞和预先存在的Th细胞的覆盖率
在常规疫苗和/或感染各种不同疾病时产生的记忆Th细胞
在没有激活有害的自身反应性T细胞的情况下,在人的一生中感染病原体。这些
“非我”Th细胞应激活B细胞并诱导产生治疗效应
人类中针对病理性Aβ和Tau的抗体,与非人类灵长类动物中的类似。
完成对老年猴子的研究以及AG060965安全/毒理学研究的数据
患病小鼠应大力支持我们的IND提交的人类首例预防性双重试验
一种基于血液、脑脊液、脑研究的针对有心肌梗塞风险或更早风险的健康人的β/tau疫苗
生物标志物。
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:
$ 41.95万 - 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:
$ 41.95万 - 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:
$ 41.95万 - 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:
$ 41.95万 - 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:
$ 41.95万 - 项目类别:
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
- 批准号:
10162389 - 财政年份:2019
- 资助金额:
$ 41.95万 - 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:
$ 41.95万 - 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:
$ 41.95万 - 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:
$ 41.95万 - 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:
$ 41.95万 - 项目类别:
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