Mechanistic evaluation of mast cell agonists combined with TLR, NOD and STING agonists.

肥大细胞激动剂联合 TLR、NOD 和 STING 激动剂的机制评估。

基本信息

  • 批准号:
    10657847
  • 负责人:
  • 金额:
    $ 64.52万
  • 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:
    2023-01-03 至 2027-12-31
  • 项目状态:
    未结题

项目摘要

ABSTRACT Subunit vaccines are safer and can more broadly be applied across the population then other vaccine formulations such as live-attenuated. However, subunit antigens are often poorly antigenic and require formulation with an immune stimulating adjuvant to garner protection. Additionally, some vaccines require more than one adjuvant, necessitating combined adjuvants to stimulate a protective response. Also, a combined adjuvant could decrease vaccination boosts and provide longer protection. One avenue to evaluate combined adjuvants is with mast cell (MC) agonists. MCs are throughout the body and reside at many interfaces of the host and the environment. When activated MCs recruit monocytes and leukocytes to the local area and help to promote an adaptive response. MC agonists combined with toll-like receptor (TLR), nucleotide-binding oligomerization domain-containing protein 2 (NOD-2), or stimulators of interferon genes (STING) agonists should elicit not only a humoral response, but also a cellular response to create an efficacious and effective vaccine. Herein we will evaluate combined MC agonists with TLR, NOD-2 or STING agonist to identify synergistic pairs. Pairs will be evaluated in mice and human cells as well as with cells from collaborative cross (CC) strains. The CC strains are a large panel of recombinant inbred mouse strains with genetic variation that can mimic the human population as well as give insight into genetic variables that contribute to adjuvant mechanism. To ensure that the adjuvants are co-delivered as well as offer dose sparring, storage outside the cold chain and controlled release of adjuvant, we will formulate them into acetalated dextran (Ac-DEX) microparticles. Ac-DEX formulations have illustrated enhanced delivery of STING, NOD-2, TLR and MC agonists in vitro and in vivo, above that of other carriers like liposomes or PLGA particles. The best identified adjuvant combination will be evaluated in a mouse model of a vaccinia vaccine with subunit antigen BR8. We will use pattern recognition receptor (PRR) knock-out mice as well as cell deficient mice to elucidate aspects of the combination adjuvant's mechanism. Additionally, we will employ genetic sequencing tools to mechanistically identify the combination adjuvants mechanism.
摘要

项目成果

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Kristy M Ainslie其他文献

Kristy M Ainslie的其他文献

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{{ truncateString('Kristy M Ainslie', 18)}}的其他基金

Diversity Supplement - Formulation to Generate Tolerance Towards Type 1 Diabetes
多样性补充剂 - 产生对 1 型糖尿病耐受性的配方
  • 批准号:
    10560761
  • 财政年份:
    2021
  • 资助金额:
    $ 64.52万
  • 项目类别:
Tunable Temporal Drug Release for Optimized Synergistic Combination Therapy of Glioblastoma
可调节的时间药物释放,用于优化胶质母细胞瘤的协同联合治疗
  • 批准号:
    10449370
  • 财政年份:
    2021
  • 资助金额:
    $ 64.52万
  • 项目类别:
Formulation to Generate Tolerance Towards Type 1 Diabetes
产生对 1 型糖尿病耐受性的配方
  • 批准号:
    10436981
  • 财政年份:
    2021
  • 资助金额:
    $ 64.52万
  • 项目类别:
Formulation to Generate Tolerance Towards Type 1 Diabetes
产生对 1 型糖尿病耐受性的配方
  • 批准号:
    10713401
  • 财政年份:
    2021
  • 资助金额:
    $ 64.52万
  • 项目类别:
Tunable Temporal Drug Release for Optimized Synergistic Combination Therapy of Glioblastoma
可调节的时间药物释放,用于优化胶质母细胞瘤的协同联合治疗
  • 批准号:
    10675073
  • 财政年份:
    2021
  • 资助金额:
    $ 64.52万
  • 项目类别:
Formulation to Generate Tolerance Towards Type 1 Diabetes
产生对 1 型糖尿病耐受性的配方
  • 批准号:
    10310642
  • 财政年份:
    2021
  • 资助金额:
    $ 64.52万
  • 项目类别:
Formulation to Generate Tolerance Towards Type 1 Diabetes
产生对 1 型糖尿病耐受性的配方
  • 批准号:
    10615119
  • 财政年份:
    2021
  • 资助金额:
    $ 64.52万
  • 项目类别:
Tunable Temporal Drug Release for Optimized Synergistic Combination Therapy of Glioblastoma
可调节的时间药物释放,用于优化胶质母细胞瘤的协同联合治疗
  • 批准号:
    10309049
  • 财政年份:
    2021
  • 资助金额:
    $ 64.52万
  • 项目类别:
Optimizing a Universal Influenza Subunit Nano/Microparticulate Vaccine
优化通用流感亚单位纳米/微粒疫苗
  • 批准号:
    10328236
  • 财政年份:
    2020
  • 资助金额:
    $ 64.52万
  • 项目类别:
Optimizing a Universal Influenza Subunit Nano/Microparticulate Vaccine
优化通用流感亚单位纳米/微粒疫苗
  • 批准号:
    10540741
  • 财政年份:
    2020
  • 资助金额:
    $ 64.52万
  • 项目类别:

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  • 批准号:
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    $ 64.52万
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  • 批准号:
    9305008
  • 财政年份:
    2016
  • 资助金额:
    $ 64.52万
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  • 批准号:
    8054408
  • 财政年份:
    2010
  • 资助金额:
    $ 64.52万
  • 项目类别:
Angiogenesis antagonist plus CD40-TLR agonist adjuvant combination vaccine
血管生成拮抗剂加CD40-TLR激动剂佐剂组合疫苗
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  • 财政年份:
    2010
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TLR 激动剂佐剂修饰的疟疾疫苗
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  • 财政年份:
    2007
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    $ 64.52万
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    2007
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