Mechanisms of vaccine immunity against coccidioidomycosis

球孢子菌病疫苗免疫机制

基本信息

  • 批准号:
    10584260
  • 负责人:
  • 金额:
    $ 53.58万
  • 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:
    2023-02-01 至 2028-01-31
  • 项目状态:
    未结题

项目摘要

ABSTRACT Coccidioidomycosis is a re-emerging infection that NIH has prioritized for vaccine prevention. An experimental vaccine of live attenuated spores is highly protective after intranasal delivery. We propose to study this vaccine to define mechanisms by which lung epithelium regulates durable mucosal T cell immunity. Resistance against inhaled microbes is thought to reside within tissue-resident memory (TRM) cells, but little is known about how this intranasal vaccine induces lung TRM. Our preliminary data reveal that the vaccine elicits protective, Coccidioides endoglucanase 2 (C-Eng2) specific CD4+ T cells and that bronchiolar club cells and Ca++ calcineurin signaling in the cells are needed to mobilize inflammatory and T cells in response to vaccine. We also find that Microfold (M) cells descend from the bronchiolar club cells and facilitate T cell priming in response to the vaccine. From these preliminary data, we hypothesize that bronchiolar club cells and M cells regulate mucosal cellular immunity in response to intranasal vaccine. To test this hypothesis, we have created innovative tools: (i) transgenic mice to deplete epithelial cell subsets or their products to further define their role in inducing immunity; (ii) C-Eng2 specific tetramers to track and analyze protective CD4+ T cells and TRM in C57BL6 mice; and (iii) methods to isolate and culture human lung epithelial cells to translate results from mice to humans. We propose three aims to test our hypothesis. In Aim 1, we will elucidate early stages of the inflammatory response to intranasal vaccine regulated by bronchiolar club cells and M cells; in Aim 2, we will identify lung epithelial cell receptors - dectin-1, DUOX1 and DUOXA1 - and downstream PLCG2 that may sense intranasal vaccine and signal via Ca++ and calcineurin to mobilize mucosal immunity; and in Aim 3, we will define mechanisms of vaccine-induced durable mucosal immunity by studying lung TRM and the regulatory role of lung epithelium. In sum, we address the unmet need of vaccination against coccidioidomycosis. Our work is significant as it will define mechanisms by which a promising vaccine establishes T cell immunity at the lung mucosa. Results will identify tactics useful for other vaccine immunogens given intranasally, including subunit vaccines. The work will define correlates of immunity needed to advance this attenuated vaccine or next generation subunit vaccines against this high priority pathogen. The work will be done with state-of-the-art, cutting-edge tools. Our team of PI and Co-I’s will let us translate results from mouse to human, with tools and reagents for human lung epithelium.
摘要

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 }}

BRUCE Steven KLEIN其他文献

BRUCE Steven KLEIN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('BRUCE Steven KLEIN', 18)}}的其他基金

Mechanisms of Vaccine Immunity against Coccidioidomycosis
球孢子菌病疫苗免疫机制
  • 批准号:
    10591641
  • 财政年份:
    2022
  • 资助金额:
    $ 53.58万
  • 项目类别:
Mode of Action Core
行动模式核心
  • 批准号:
    10571218
  • 财政年份:
    2019
  • 资助金额:
    $ 53.58万
  • 项目类别:
Mode of Action Core
行动模式核心
  • 批准号:
    10592385
  • 财政年份:
    2019
  • 资助金额:
    $ 53.58万
  • 项目类别:
Lung epithelial cell regulation of immunity to inhaled fungi
肺上皮细胞对吸入真菌免疫的调节
  • 批准号:
    10222492
  • 财政年份:
    2018
  • 资助金额:
    $ 53.58万
  • 项目类别:
Lung epithelial cell regulation of immunity to inhaled fungi
肺上皮细胞对吸入真菌免疫的调节
  • 批准号:
    10451274
  • 财政年份:
    2018
  • 资助金额:
    $ 53.58万
  • 项目类别:
Lung epithelial cell regulation of immunity to inhaled fungi
肺上皮细胞对吸入真菌免疫的调节
  • 批准号:
    9975090
  • 财政年份:
    2018
  • 资助金额:
    $ 53.58万
  • 项目类别:
Combination Adjuvants to Program Durable Immunity to Respiratory Viral and Fungal Pathogens
组合佐剂可对呼吸道病毒和真菌病原体产生持久免疫
  • 批准号:
    10614603
  • 财政年份:
    2016
  • 资助金额:
    $ 53.58万
  • 项目类别:
Combination Adjuvants to Program Durable Immunity to Respiratory Viral and Fungal Pathogens
组合佐剂可对呼吸道病毒和真菌病原体产生持久免疫
  • 批准号:
    10224468
  • 财政年份:
    2016
  • 资助金额:
    $ 53.58万
  • 项目类别:
Combination Adjuvants to Program Durable Immunity to Respiratory Viral and Fungal Pathogens
组合佐剂可对呼吸道病毒和真菌病原体产生持久免疫
  • 批准号:
    10448406
  • 财政年份:
    2016
  • 资助金额:
    $ 53.58万
  • 项目类别:
Combination Adjuvants to Program Durable Immunity to Respiratory Viral and Fungal Pathogens
组合佐剂可对呼吸道病毒和真菌病原体产生持久免疫
  • 批准号:
    10544356
  • 财政年份:
    2016
  • 资助金额:
    $ 53.58万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 53.58万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 53.58万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 53.58万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 53.58万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 53.58万
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 53.58万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 53.58万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 53.58万
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 53.58万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 53.58万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了