Novel multivalent viral vectored tuberculosis vaccines targeting lung immunity
针对肺部免疫的新型多价病毒载体结核疫苗
基本信息
- 批准号:10738913
- 负责人:
- 金额:$ 18.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-23 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAdvanced DevelopmentAerosolsAntibodiesAntibody ResponseAntigensArenavirusAttenuatedBacterial InfectionsCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCD8B1 geneCell surfaceCellular ImmunityCessation of lifeChildhoodCommunicable DiseasesComplexDataDevelopmentDiagnosisDiseaseEngineeringExhibitsGenomeGoalsImmune responseImmunityImmunologicsIndividualInfectionKnowledgeLicensingLungMemoryModelingMusMycobacterium bovisMycobacterium tuberculosisMycobacterium tuberculosis antigensOpen Reading FramesPhasePichinde virusPopulationPreventionPreventive vaccineProteinsPulmonary TuberculosisRNARecombinantsResearchRouteSafetyStructure of parenchyma of lungT cell responseT-LymphocyteTestingTherapeuticTuberculosisTuberculosis VaccinesTuberculosis diagnosisVaccinationVaccine ResearchVaccinesViral VectorVirulentadaptive immune responseantigen testantigen-specific T cellsdesignefficacy evaluationfightingimmunogenicityimprovedinnovationlatent infectionlifetime risklong term memorymouse modelnext generationnovelpathogenpreclinical evaluationpreventprotective efficacyreactivation from latencyrecruitresearch clinical testingtuberculosis immunityvaccine candidatevaccine developmentvaccine efficacyvaccine platformvaccine responsevector
项目摘要
Abstract
Title: Novel multivalent viral vectored tuberculosis vaccines targeting lung immunity
Tuberculosis (TB) persists as the deadliest bacterial infection, with more than 10 million new cases of active TB
diagnosed and 1.5 million deaths attributed to TB worldwide each year, because there is no highly effective
preventative vaccine. Mycobacterium tuberculosis (Mtb) also causes asymptomatic latent infections in ~25% of
the world’s population. Latently infected individuals have a 10% lifetime risk of developing active TB disease.
Vaccines that prevent pulmonary Mtb infection, limit reactivation from latency and/or therapeutically treat active
TB disease are urgently needed. The objective of this R21 proposal is to explore the unique immunological
features of an innovative Pichinde virus (PICV)-based vaccine platform combined with novel Mtb antigens to
develop next generation TB vaccines. PICV is a non-pathogenic arenavirus with a bi-segmented RNA genome.
The proposal exploits a recombinant PICV engineered with three RNA segments, rP18tri, which can encode two
additional open-reading frames (ORFs) to express antigens. The rP18tri platform is safe, versatile and induces
balanced antibody and T cell responses. Moreover, the rP18tri platform is simple to modify to produce a variety
of multivalent antigens, which enables rapid analysis of candidates to identify those antigens that induce the
greatest protection. The proposed research will test the hypothesis that optimized multivalent antigens delivered
intranasally via the rP18tri viral vector platform will induce robust protective immunity against pulmonary Mtb
infection. Preliminary data from proof-of-concept studies establish that rP18tri-based TB vaccines can be
efficiently generated, induce strong antigen-specific T cell immunity and protect against pulmonary Mtb infection
in a mouse aerosol challenge model. In this R21 proposal, we will generate additional rP18tri vector-based
multivalent TB vaccine candidates with novel immunogens (Aim 1), evaluate antibody as well as systemic and
lung tissue-resident T cell responses induced by these vaccines in mice (Aim 2), and assess the efficacy of these
vaccines for prevention of Mtb infection in a mouse model (Aim 3). The study is significant because it is
expected to produce at least one viral vectored multivalent TB vaccine candidate with demonstrated safety and
efficacy in mice to be advanced to the next phases of preclinical and clinical evaluations. The study is also
expected to generate new knowledge on protective immunity induced by novel Mtb antigens, which will guide
the design of next generation TB vaccines, and to advance development of the PICV vector platform, which will
expand the toolbox for fighting infectious diseases.
摘要
标题:靶向肺免疫的新型多价病毒载体结核疫苗
结核病(TB)仍然是最致命的细菌感染,有1000多万新的活动性结核病病例
全世界每年有150万人因结核病确诊和死亡,因为没有高效的
预防性疫苗结核分枝杆菌(Mtb)也会在约25%的人中引起无症状的潜伏感染。
世界人口。潜伏感染者有10%的终生风险发展为活动性结核病。
预防肺Mtb感染、限制潜伏期再活化和/或治疗性治疗活性Mtb的疫苗
结核病是迫切需要的。这项R21提案的目的是探索独特的免疫学
一种基于皮钦德病毒(PICV)的创新疫苗平台与新型Mtb抗原相结合,
开发下一代结核病疫苗。PICV是一种具有双节段RNA基因组的非致病性沙粒病毒。
该提案利用了一种重组PICV,该重组PICV具有三个RNA片段rP18tri,其可以编码两个
额外的开放阅读框(ORF)以表达抗原。rP18tri平台安全、通用,
平衡的抗体和T细胞反应。此外,rP18tri平台易于修改以产生多种
多价抗原,这使得能够快速分析候选物,以鉴定诱导免疫应答的那些抗原。
最大的保护。拟议的研究将测试优化的多价抗原递送的假设,
通过rP18tri病毒载体平台鼻内给药将诱导针对肺Mtb的强大保护性免疫
感染来自概念验证研究的初步数据确定,基于rP18trii的TB疫苗可以用于治疗结核病。
有效地产生,诱导强抗原特异性T细胞免疫并保护免受肺结核感染
在小鼠气溶胶激发模型中。在此R21提案中,我们将生成额外的基于rP18tri的矢量
具有新型免疫原的多价结核病候选疫苗(目的1),评估抗体以及全身和
这些疫苗在小鼠中诱导的肺组织驻留T细胞反应(目的2),并评估这些疫苗的功效
在小鼠模型中预防Mtb感染的疫苗(目的3)。这项研究意义重大,因为它
预期产生至少一种经证实安全性的病毒载体多价TB疫苗候选物,
在小鼠中的有效性被推进到下一阶段的临床前和临床评价。该研究也是
预计将产生关于新型Mtb抗原诱导的保护性免疫的新知识,这将指导
设计下一代结核病疫苗,并推进PICV载体平台的开发,
扩大防治传染病的工具箱。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
YUYING LIANG其他文献
YUYING LIANG的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('YUYING LIANG', 18)}}的其他基金
Viral Vectored COVID-19 Vaccines in a Guinea Pig Perinatal Infection Model
豚鼠围产期感染模型中的病毒载体 COVID-19 疫苗
- 批准号:
10369372 - 财政年份:2021
- 资助金额:
$ 18.91万 - 项目类别:
Viral Vectored COVID-19 Vaccines in a Guinea Pig Perinatal Infection Model
豚鼠围产期感染模型中的病毒载体 COVID-19 疫苗
- 批准号:
10515662 - 财政年份:2021
- 资助金额:
$ 18.91万 - 项目类别:
Mechanism of Lassa fever virus Z protein in immune suppression and viral virulence
拉沙热病毒Z蛋白免疫抑制及病毒毒力机制
- 批准号:
9333725 - 财政年份:2017
- 资助金额:
$ 18.91万 - 项目类别:
Receptor tyrosine kinase signaling and influenza viral RNA synthesis
受体酪氨酸激酶信号传导和流感病毒RNA合成
- 批准号:
8241210 - 财政年份:2012
- 资助金额:
$ 18.91万 - 项目类别:
Receptor tyrosine kinase signaling and influenza viral RNA synthesis
受体酪氨酸激酶信号传导和流感病毒RNA合成
- 批准号:
8426084 - 财政年份:2012
- 资助金额:
$ 18.91万 - 项目类别:
Molecular determinants of virulent arenavirus infection in hosts
宿主强毒沙粒病毒感染的分子决定因素
- 批准号:
8060493 - 财政年份:2010
- 资助金额:
$ 18.91万 - 项目类别:
Molecular determinants of virulent arenavirus infection in hosts
宿主强毒沙粒病毒感染的分子决定因素
- 批准号:
8259831 - 财政年份:2010
- 资助金额:
$ 18.91万 - 项目类别:
Molecular determinants of virulent arenavirus infection in hosts
宿主强毒沙粒病毒感染的分子决定因素
- 批准号:
7889110 - 财政年份:2010
- 资助金额:
$ 18.91万 - 项目类别:
Molecular determinants of virulent arenavirus infection in hosts
宿主强毒沙粒病毒感染的分子决定因素
- 批准号:
8460799 - 财政年份:2010
- 资助金额:
$ 18.91万 - 项目类别:
Molecular determinants of virulent arenavirus infection in hosts
宿主强毒沙粒病毒感染的分子决定因素
- 批准号:
8651859 - 财政年份:2010
- 资助金额:
$ 18.91万 - 项目类别:
相似海外基金
ADVANCED DEVELOPMENT OF LQ A LIPOSOME-BASED SAPONIN-CONTAINING ADJUVANT FOR USE IN PANSARBECOVIRUS VACCINES
用于 Pansarbecovirus 疫苗的 LQ A 脂质体含皂苷佐剂的先进开发
- 批准号:
10935820 - 财政年份:2023
- 资助金额:
$ 18.91万 - 项目类别:
ADVANCED DEVELOPMENT OF BBT-059 AS A RADIATION MEDICAL COUNTERMEASURE FOR DOSING UP TO 48H POST EXPOSURE"
BBT-059 的先进开发,作为辐射医学对策,可在暴露后 48 小时内进行给药”
- 批准号:
10932514 - 财政年份:2023
- 资助金额:
$ 18.91万 - 项目类别:
Advanced Development of a Combined Shigella-ETEC Vaccine
志贺氏菌-ETEC 联合疫苗的先进开发
- 批准号:
10704845 - 财政年份:2023
- 资助金额:
$ 18.91万 - 项目类别:
Advanced development of composite gene delivery and CAR engineering systems
复合基因递送和CAR工程系统的先进开发
- 批准号:
10709085 - 财政年份:2023
- 资助金额:
$ 18.91万 - 项目类别:
Advanced development and validation of an in vitro platform to phenotype brain metastatic tumor cells using artificial intelligence
使用人工智能对脑转移肿瘤细胞进行表型分析的体外平台的高级开发和验证
- 批准号:
10409385 - 财政年份:2022
- 资助金额:
$ 18.91万 - 项目类别:
ADVANCED DEVELOPMENT OF A VACCINE FOR PANDEMIC AND PRE-EMERGENT CORONAVIRUSES
针对大流行和突发冠状病毒的疫苗的高级开发
- 批准号:
10710595 - 财政年份:2022
- 资助金额:
$ 18.91万 - 项目类别:
Advanced development and validation of an in vitro platform to phenotype brain metastatic tumor cells using artificial intelligence
使用人工智能对脑转移肿瘤细胞进行表型分析的体外平台的高级开发和验证
- 批准号:
10630975 - 财政年份:2022
- 资助金额:
$ 18.91万 - 项目类别:
ADVANCED DEVELOPMENT OF A VACCINE CANDIDATE FOR STAPHYLOCOCCUS AUREUS INFECTION
金黄色葡萄球菌感染候选疫苗的高级开发
- 批准号:
10710588 - 财政年份:2022
- 资助金额:
$ 18.91万 - 项目类别:
ADVANCED DEVELOPMENT OF A VACCINE FOR PANDEMIC AND PRE-EMERGENT CORONAVIRUSES
针对大流行和突发冠状病毒的疫苗的高级开发
- 批准号:
10788051 - 财政年份:2022
- 资助金额:
$ 18.91万 - 项目类别: