An adjuvant that promotes TH1/TH17 and CD8 T cells in a tuberculosis vaccine

一种在结核疫苗中促进 TH1/TH17 和 CD8 T 细胞的佐剂

基本信息

  • 批准号:
    8994259
  • 负责人:
  • 金额:
    $ 112.49万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-02-01 至 2018-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): There are two major components of effective vaccines: adjuvants and antigens. The adjuvant for a vaccine must induce the immune responses that are protective, while the antigens must be those against which an immune response can provide protection from infection or disease. Most currently available adjuvants for humans, of which there are very few, induce antibody responses and primarily Th2 T cell responses. For many infections, including M. tuberculosis, Th1 CD4 T cell response and a cytotoxic or cytokine-producing CD8 T cell response are needed. Adjuvants that can induce such responses against subunit proteins and are also safe are urgently needed to tackle the most stubborn infectious diseases. Here, we propose to optimize a promising new adjuvant developed by Statens Serum Institute (SSI), CAF09, which builds on the CAF platform of cationic nanoparticles composed of bioactive lipids. This adjuvant induces both CD4 (Th1, Th17) and CD8 T cells. Optimization of CAF09 formulation and route of vaccination will be performed, using an established subunit vaccine, H56, which was developed by SSI and has been demonstrated to provide protection in several animal models, including non-human primates. Following optimization, the best candidates, based on mouse studies, will be tested for immunogenicity in non-human primates, to provide better translation to humans. The best formulation of CAF09/H56 will be scaled up and toxicity and stability studies will be performed. Finally, one formulation of CAF09/H56, as determined by the iterative studies in mice and monkeys, will be tested in a rigorous non-human primate M. tuberculosis challenge model. These studies will provide the crucial pre-clinical data for moving CAF09/H56 forward into human clinical trials as an improved TB vaccine candidate.
描述(申请人提供):有效疫苗有两种主要成分:佐剂和抗原。疫苗的佐剂必须诱导保护性的免疫应答,而抗原必须是免疫应答可以提供保护免受感染或疾病的抗原。大多数目前可用于人类的佐剂(其中很少)诱导抗体应答并且主要是Th 2 T细胞应答。对于包括M.需要Th 1 CD 4 T细胞应答和细胞毒性或产生嘌呤的CD 8 T细胞应答。迫切需要能够诱导针对亚基蛋白的这种反应并且也是安全的佐剂来应对最顽固的感染性疾病。在这里,我们建议优化Statens血清研究所(SSI)开发的一种有前途的新佐剂CAF 09,它建立在由生物活性脂质组成的阳离子纳米颗粒的CAF平台上。该佐剂诱导CD 4(Th 1,Th 17)和CD 8 T细胞。将使用已确定的亚单位疫苗H56进行CAF 09制剂和疫苗接种途径的优化,H56由SSI开发,并已证明在几种动物模型(包括非人灵长类动物)中提供保护。在优化之后,基于小鼠研究的最佳候选物将在非人灵长类动物中进行免疫原性测试,以提供更好的人类翻译。CAF 09/H56的最佳制剂将按比例放大,并将进行毒性和稳定性研究。最后,将在严格的非人灵长类动物M.结核病挑战模型这些研究将为CAF 09/H56作为改进的结核病候选疫苗进入人体临床试验提供关键的临床前数据。

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 }}

JoAnne L. Flynn其他文献

This information is current as Infection Mycobacterium tuberculosis during Antimicrobial Responses with Caseation Mediated − Early Host Immunity Control of Lesion Sterilization by Balancing Computational Modeling Predicts IL-10
此信息是当前的感染结核分枝杆菌在干酪介导的抗菌反应期间通过平衡计算模型预测 IL-10 进行病灶灭菌的早期宿主免疫控制
  • DOI:
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Nicholas A. Cilfone;Christopher B Ford;Simeone Marino;Joshua T Mattila;H. Gideon;JoAnne L. Flynn;Denise E. Kirschner;J. Linderman
  • 通讯作者:
    J. Linderman
Modeling pathogen and host: <em>in vitro</em>, <em>in vivo</em> and <em>in silico</em> models of latent <em>Mycobacterium tuberculosis</em> infection
  • DOI:
    10.1016/j.ddmod.2005.05.019
  • 发表时间:
    2005-06-01
  • 期刊:
  • 影响因子:
  • 作者:
    P. Ling Lin;Denise Kirschner;JoAnne L. Flynn
  • 通讯作者:
    JoAnne L. Flynn
emIn silico/em identification and synthesis of a multi-drug loaded MOF for treating tuberculosis
  • DOI:
    10.1016/j.jconrel.2022.10.024
  • 发表时间:
    2022-12-01
  • 期刊:
  • 影响因子:
    11.500
  • 作者:
    Abhinav P. Acharya;Kutay B. Sezginel;Hannah P. Gideon;Ashlee C. Greene;Harrison D. Lawson;Sahil Inamdar;Ying Tang;Amy J. Fraser;Kush V. Patel;Chong Liu;Nathaniel L. Rosi;Stephen Y. Chan;JoAnne L. Flynn;Christopher E. Wilmer;Steven R. Little
  • 通讯作者:
    Steven R. Little
This information is current as Infection in BALB / c Mice tuberculosis Mycobacterium the Control of Chronic The Chemokine Receptor CXCR 3 Attenuates
此信息当前为 BALB / c 小鼠结核分枝杆菌感染控制慢性趋化因子受体 CXCR 3 减弱
  • DOI:
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    0
  • 作者:
    S. Chakravarty;Jiayong Xu;Bao Lu;Craig Gerard;JoAnne L. Flynn;John Chan
  • 通讯作者:
    John Chan
SARS-CoV-2 Receptor ACE2 is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Enriched in Specific Cell Subsets Across Tissues
SARS-CoV-2 受体 ACE2 是人气道上皮细胞中的干扰素刺激基因,富含组织中的特定细胞亚群
  • DOI:
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Carly N Ziegler;Samuel J. Allon;Sarah K Nyquist;Ian M. Mbano;Vincent N Miao;Yuming Cao;Ashraf S. Yousif;Julia Bals;B. Hauser;J. Feldman;Christoph Muus;Marc H Wadsworth Ii;S. Kazer;T. Hughes;B. Doran;G. J. Gatter;Marko Vukovic;C. Tzouanas;F. Taliaferro;Zhiru Guo;Jennifer P. Wang;Daniel F Dwyer;K. Buchheit;Joshua A. Boyce;Nora A. Barrett;T. Laidlaw;Shaina L. Carroll;Lucrezia Colonna;V. Tkachev;Alison Yu;Henqi Betty Zheng;H. Gideon;Caylin G. Winchell;P. Lin;Bonnie Berger;A. Leslie;JoAnne L. Flynn;Sarah M Fortune;R. Finberg;Leslie S. Kean;Manuel Garber;Aaron Schmidt;D. Lingwood;A. Shalek;J. Ordovas;Hca Lung Biological Network
  • 通讯作者:
    Hca Lung Biological Network

JoAnne L. Flynn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('JoAnne L. Flynn', 18)}}的其他基金

Enhancing cytotoxic lymphocytes in a TB vaccine strategy
在结核病疫苗策略中增强细胞毒性淋巴细胞
  • 批准号:
    10462928
  • 财政年份:
    2022
  • 资助金额:
    $ 112.49万
  • 项目类别:
Enhancing cytotoxic lymphocytes in a TB vaccine strategy
在结核病疫苗策略中增强细胞毒性淋巴细胞
  • 批准号:
    10580073
  • 财政年份:
    2022
  • 资助金额:
    $ 112.49万
  • 项目类别:
Dissecting the pathogenesis of HIV-TB Immune reconstitution inflammatory syndrome
剖析 HIV-TB 免疫重建炎症综合征的发病机制
  • 批准号:
    10097199
  • 财政年份:
    2020
  • 资助金额:
    $ 112.49万
  • 项目类别:
Dissecting the pathogenesis of HIV-TB Immune reconstitution inflammatory syndrome
剖析 HIV-TB 免疫重建炎症综合征的发病机制
  • 批准号:
    10451735
  • 财政年份:
    2020
  • 资助金额:
    $ 112.49万
  • 项目类别:
Dissecting the pathogenesis of HIV-TB Immune reconstitution inflammatory syndrome
剖析 HIV-TB 免疫重建炎症综合征的发病机制
  • 批准号:
    10667439
  • 财政年份:
    2020
  • 资助金额:
    $ 112.49万
  • 项目类别:
Dissecting the pathogenesis of HIV-TB Immune reconstitution inflammatory syndrome
剖析 HIV-TB 免疫重建炎症综合征的发病机制
  • 批准号:
    10240712
  • 财政年份:
    2020
  • 资助金额:
    $ 112.49万
  • 项目类别:
Predicting protective T-cell responses in Tuberculosis using a systems biology approach
使用系统生物学方法预测结核病中的保护性 T 细胞反应
  • 批准号:
    9072491
  • 财政年份:
    2016
  • 资助金额:
    $ 112.49万
  • 项目类别:
The Effects of M. tuberculosisInfection on Lung Microbiome in Macaques
结核分枝杆菌感染对猕猴肺部微生物组的影响
  • 批准号:
    9018134
  • 财政年份:
    2016
  • 资助金额:
    $ 112.49万
  • 项目类别:
An adjuvant that promotes TH1/TH17 and CD8 T cells in a tuberculosis vaccine
一种在结核疫苗中促进 TH1/TH17 和 CD8 T 细胞的佐剂
  • 批准号:
    8607041
  • 财政年份:
    2013
  • 资助金额:
    $ 112.49万
  • 项目类别:
An adjuvant that promotes TH1/TH17 and CD8 T cells in a tuberculosis vaccine
一种在结核疫苗中促进 TH1/TH17 和 CD8 T 细胞的佐剂
  • 批准号:
    9208083
  • 财政年份:
    2013
  • 资助金额:
    $ 112.49万
  • 项目类别:

相似海外基金

Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
  • 批准号:
    495434
  • 财政年份:
    2023
  • 资助金额:
    $ 112.49万
  • 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
  • 批准号:
    10642519
  • 财政年份:
    2023
  • 资助金额:
    $ 112.49万
  • 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
  • 批准号:
    10586596
  • 财政年份:
    2023
  • 资助金额:
    $ 112.49万
  • 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
  • 批准号:
    10590479
  • 财政年份:
    2023
  • 资助金额:
    $ 112.49万
  • 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
  • 批准号:
    23K06011
  • 财政年份:
    2023
  • 资助金额:
    $ 112.49万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
  • 批准号:
    10682117
  • 财政年份:
    2023
  • 资助金额:
    $ 112.49万
  • 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
  • 批准号:
    10708517
  • 财政年份:
    2023
  • 资助金额:
    $ 112.49万
  • 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
  • 批准号:
    10575566
  • 财政年份:
    2023
  • 资助金额:
    $ 112.49万
  • 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
  • 批准号:
    23K15696
  • 财政年份:
    2023
  • 资助金额:
    $ 112.49万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
  • 批准号:
    23K15867
  • 财政年份:
    2023
  • 资助金额:
    $ 112.49万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了