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

基本信息

  • 批准号:
    10580073
  • 负责人:
  • 金额:
    $ 77.35万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-02-25 至 2027-01-31
  • 项目状态:
    未结题

项目摘要

ABSTRACT: Currently BCG is the most widely administered vaccine worldwide against tuberculosis (TB). Yet, TB remains one of the most common causes of death from an infectious disease globally underscoring its limited efficacy. We have shown that BCG’s vaccine efficacy can be improved if administered by a different route or dose. In fact, intravenous BCG vaccination resulted in 90% protection in a non-human primate model of TB but this method is impractical to conduct on a population scale. Features associated with protection include the presence of CD8 and CD4 T cells in the airways and lung resident T cells. In this proposal we plan to mimic this immune response and improve upon the existing BCG vaccine in a strategy that we call “enhanced prime and pull”. We propose to use N-803, an IL-15 agonist, to enhance the frequency of innate CD8 cells and boost the effects of high dose, intradermal BCG. This is followed by a dose of aerosolized BCG to pull vaccine-induced immune cells into the areas and propagate resident T cells in the lungs. Using an animal model that recapitulates human TB, we will utilized state-of-the-art modern tools such as PET CT, large scale immunologic profiling both at a transcriptional and flow cytometric level and machine learning techniques. Immunogenicity in blood and airway immune cells will examined among vaccine and control groups prior to infection with Mycobacterium tuberculosis (Aim 1). After infection, we will then compare the ability of the vaccine regimen to prevent infection and/or lower bacterial burden compared to controls (Aim 2). We will examine the immune responses (including the presence of tissue resident T cells) in the granuloma, lungs and mediastinal lymph nodes in the context of bacterial burden among vaccinated and control groups. Lastly, machine learning techniques will be used to identify immune parameters that correlate with protection in the context of vaccines. The proposed studies are likely to reveal important information about the role of innate cytotoxic CD8 cell and their role in vaccine induced protection and mechanisms of recruiting mucosal immune responses. We may also gain important insights into key surrogate markers of protection sorely needed in the TB field.
摘要:目前,卡介苗是世界上使用最广泛的疫苗

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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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

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{{ 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:
    $ 77.35万
  • 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:
    $ 77.35万
  • 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:
    $ 77.35万
  • 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:
    $ 77.35万
  • 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:
    $ 77.35万
  • 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:
    $ 77.35万
  • 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:
    $ 77.35万
  • 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:
    $ 77.35万
  • 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:
    8994259
  • 财政年份:
    2013
  • 资助金额:
    $ 77.35万
  • 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:
    $ 77.35万
  • 项目类别:

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