Development of a novel adjuvant strategy enabled by modulation of the physical properties of fungal mannans

通过调节真菌甘露聚糖的物理特性开发新型佐剂策略

基本信息

  • 批准号:
    10338399
  • 负责人:
  • 金额:
    $ 77.79万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-17 至 2026-08-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Vaccines represent a highly effective public health measure to protect individuals from infectious diseases. Many vaccines work by inducing antigen-specific antibodies that neutralize the pathogen or its products and promote their clearance. Vaccines based on protein antigens usually require the addition of adjuvants to enhance potency, breadth and duration of the antigen-specific adaptive immune response. Adjuvants promote vaccine antigen immunogenicity by activating receptors of the innate immune system called pattern-recognition receptors (PRRs) and/or modulating antigen pharmacokinetics. Aluminum salts are the most common adjuvants in FDA- approved vaccines. Recently, vaccines including adjuvants that target specific PRRs, in particular toll-like receptor (TLR)4 and TLR9, have also been approved by the FDA, paving the way for the development of molecularly defined adjuvants. Investigating the potential of additional PRRs as adjuvant targets is of paramount important to expand our vaccine toolbox and probe how different modalities of innate immune cell activation impact the adaptive immune response. Here, we propose to use the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein as a model antigen to test a new adjuvant formulation that contains fungal ligands that target the PRR Dectin-2. Our preliminary results show that mannans (fungal cell wall polysaccharides isolated from Candia albicans) alone or formulated with aluminum hydroxide enhance the immunogenicity of pre-fusion stabilized, Spike trimers in mouse models of immunization. In particular, mannan formulations, compared to aluminum hydroxide only, induce an early increase in anti-Spike antibody levels, potentiate the induction of SARS-CoV-2 neutralizing antibodies, broaden the Spike epitopes that are targeted and favor the switch towards immunoglobulin subclasses associated with higher effector functions and reduced risk of vaccine-associated enhanced respiratory disease (VAERD). Here we hypothesize that mannans formulated with alumOH induce a potent and durable adaptive immune response to SARS-CoV-2 Spike by inducing specific innate immune pathways and activation programs. By combining detailed immunogenicity and mechanistic analyses, our proposal will define a novel adjuvant formulation for SARS-CoV-2 Spike and potentially other viral glycoproteins as well as shed new light on the biology of Dectin-2.
项目总结 疫苗是保护个人免受传染病侵袭的一种非常有效的公共卫生措施。许多 疫苗的工作原理是诱导抗原特异性抗体,中和病原体或其产物,促进 他们的许可。基于蛋白质抗原的疫苗通常需要添加佐剂来增强 抗原特异性适应性免疫反应的效力、广度和持续时间。佐剂促进疫苗 通过激活称为模式识别受体的先天免疫系统受体来实现抗原免疫原性 (PRRS)和/或调节抗原药代动力学。铝盐是FDA最常见的佐剂- 批准的疫苗。最近,包括针对特定PRR的佐剂的疫苗,特别是类似Toll的疫苗 受体(TLR)4和TLR9也已获得FDA的批准,为开发 分子定义的佐剂。研究额外的PRR作为佐剂靶点的潜力至关重要 重要的是要扩展我们的疫苗工具箱,并探索不同的天然免疫细胞激活方式 影响适应性免疫反应。在这里,我们建议使用严重急性呼吸综合征 以冠状病毒2型(SARS-CoV-2)刺突蛋白为模型抗原,测试一种新的佐剂制剂,该制剂含有 靶向PRR Dectin-2的真菌配体。我们的初步结果表明,甘露聚糖(真菌细胞壁 从白色念珠菌中分离出的多糖)单独或与氢氧化铝配伍可增强 融合前的免疫原性稳定,Spike三聚体在小鼠模型中免疫。尤其是曼南 与仅使用氢氧化铝相比,配方会导致早期的抗尖峰抗体水平上升, 增强SARS-CoV-2中和抗体的诱导,拓宽靶向的尖峰表位 并且有利于向免疫球蛋白亚类的转变,这些亚类与更高的效应器功能和更少的免疫球蛋白相关 疫苗相关增强型呼吸道疾病(VAERD)的风险。在这里我们假设甘露糖 氢氧化铝制剂诱导对SARS-CoV-2刺突的有效和持久的适应性免疫反应 通过诱导特定的先天免疫途径和激活程序。通过将详细的 免疫原性和机制分析,我们的建议将定义一种新的佐剂配方 SARS-CoV-2 Spike和潜在的其他病毒糖蛋白,以及对SARS-CoV-2毒株生物学的新认识 Dectin-2。

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 }}

Ivan Zanoni其他文献

Ivan Zanoni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('Ivan Zanoni', 18)}}的其他基金

Macrophage immunometabolism controls septic shock
巨噬细胞免疫代谢控制感染性休克
  • 批准号:
    10658162
  • 财政年份:
    2023
  • 资助金额:
    $ 77.79万
  • 项目类别:
Development of a novel adjuvant strategy enabled by modulation of the physical properties of fungal mannans
通过调节真菌甘露聚糖的物理特性开发新型佐剂策略
  • 批准号:
    10490881
  • 财政年份:
    2021
  • 资助金额:
    $ 77.79万
  • 项目类别:
Development of a novel adjuvant strategy enabled by modulation of the physical properties of fungal mannans
通过调节真菌甘露聚糖的物理特性开发新型佐剂策略
  • 批准号:
    10687182
  • 财政年份:
    2021
  • 资助金额:
    $ 77.79万
  • 项目类别:
Innate control of the inflammatory process during fungal infections
真菌感染期间炎症过程的先天控制
  • 批准号:
    10434924
  • 财政年份:
    2016
  • 资助金额:
    $ 77.79万
  • 项目类别:
Innate control of the inflammatory process during fungal infections
真菌感染期间炎症过程的先天控制
  • 批准号:
    10293993
  • 财政年份:
    2016
  • 资助金额:
    $ 77.79万
  • 项目类别:
Innate control of the inflammatory process during fungal infections
真菌感染期间炎症过程的先天控制
  • 批准号:
    10641775
  • 财政年份:
    2016
  • 资助金额:
    $ 77.79万
  • 项目类别:
Innate control of the inflammatory process during fungal infections
真菌感染期间炎症过程的先天控制
  • 批准号:
    9122779
  • 财政年份:
    2016
  • 资助金额:
    $ 77.79万
  • 项目类别:
Innate control of the inflammatory process during fungal infections
真菌感染期间炎症过程的先天控制
  • 批准号:
    9232989
  • 财政年份:
    2016
  • 资助金额:
    $ 77.79万
  • 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:
    $ 77.79万
  • 项目类别:
    Fellowship
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:
    $ 77.79万
  • 项目类别:
    Continuing Grant
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:
    $ 77.79万
  • 项目类别:
    Research 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:
    $ 77.79万
  • 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:
    $ 77.79万
  • 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:
    $ 77.79万
  • 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:
    $ 77.79万
  • 项目类别:
    EU-Funded
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:
    $ 77.79万
  • 项目类别:
    Standard Grant
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:
    $ 77.79万
  • 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:
    $ 77.79万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了