A Self-Adjuvanting Virus Like Particle Vaccine Platform for Emerging Viruses

针对新兴病毒的自我佐剂病毒样颗粒疫苗平台

基本信息

项目摘要

Project Summary The goals of this R01 proposal include the molecular and immunological characterization of vaccine adjuvant activity associated with processes mediated by the protein Stimulator of Interferon Genes (STING). Vaccines comprised of inert antigen are often only weakly immunogenic and thus require co-administration of adjuvants to augment immunostimulation. Unfortunately, very few adjuvants are approved for clinical use and the mechanisms of adjuvant-associated enhancement are poorly understood. STING is a pattern recognition receptor that detects purine-containing cyclic dinucleotides (CDN) synthesized by either bacterial cyclases or the host enzyme cyclic GMP-AMP (cGAMP) synthase (cGAS) following its sensing of cytosolic DNA. Pharmacologic activation of STING greatly enhances vaccine efficacy as indicated by antibody and cell-mediated protection against diverse microbial pathogens. Furthermore, endogenously synthesized cGAMP is naturally released from cells in exosomes and virus particles. We exploited this phenomenon by constructing cell lines that express constitutively active cyclases that we then used to produce immunogenic virus-like particles (VLP). We now show that VLP derived from unrelated emerging flavi- and alphaviruses efficiently encapsulate bioactive CDN and stimulate STING-dependent activity in vivo. Since extracellular CDNs are highly susceptible to degradation and disperse quickly from the site of injection, we hypothesize that this simple approach represents a transformative technological improvement for harnessing STING-directed adjuvant effects in the draining lymph node. We also predict this will be a highly adaptable platform and propose to explore the extent to which it is applicable to potentially emerging virus types. Experimentally, this also represents a unique investigative model that will allow in vivo characterization of the innate and molecular correlates of adaptive immunity that are potentiated by targeted STING activity. We thus hypothesize that the enhancement of antigen-directed immune responses by STING-based adjuvants is functionally linked to key molecular and cellular processes that are discernable using our proposed vaccines and experimental systems. We plan to explore this using an integrated approach that uses molecular transcriptomic analysis, mouse models of immune profiling, and nonhuman primate models of viral growth and protective immunity devised by our group.
项目总结

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 }}

VICTOR Robert DEFILIPPIS其他文献

VICTOR Robert DEFILIPPIS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('VICTOR Robert DEFILIPPIS', 18)}}的其他基金

Anti-tumor efficacy of novel cGAS-STING pathway agonists
新型 cGAS-STING 通路激动剂的抗肿瘤功效
  • 批准号:
    10286612
  • 财政年份:
    2021
  • 资助金额:
    $ 76.76万
  • 项目类别:
Anti-tumor efficacy of novel cGAS-STING pathway agonists
新型 cGAS-STING 通路激动剂的抗肿瘤功效
  • 批准号:
    10430274
  • 财政年份:
    2021
  • 资助金额:
    $ 76.76万
  • 项目类别:
Mechanistic Exploration of cGAS-STING-Mediated Vaccine Enhancement
cGAS-STING 介导的疫苗增强机制探索
  • 批准号:
    10318966
  • 财政年份:
    2019
  • 资助金额:
    $ 76.76万
  • 项目类别:
Mechanistic Exploration of cGAS-STING-Mediated Vaccine Enhancement
cGAS-STING 介导的疫苗增强机制探索
  • 批准号:
    10534676
  • 财政年份:
    2019
  • 资助金额:
    $ 76.76万
  • 项目类别:
THE ROLE OF CYTOMEGALOVIRUS PHOSPHOPROTEIN 65 IN VIRUS REPLICATON IN VIVO
巨细胞病毒磷酸蛋白65在体内病毒复制中的作用
  • 批准号:
    7958465
  • 财政年份:
    2009
  • 资助金额:
    $ 76.76万
  • 项目类别:
THE ROLE OF CYTOMEGALOVIRUS PHOSPHOPROTEIN 65 IN VIRUS REPLICATON IN VIVO
巨细胞病毒磷酸蛋白65在体内病毒复制中的作用
  • 批准号:
    7715956
  • 财政年份:
    2008
  • 资助金额:
    $ 76.76万
  • 项目类别:
THE ROLE OF CYTOMEGALOVIRUS PHOSPHOPROTEIN 65 IN VIRUS REPLICATON IN VIVO
巨细胞病毒磷酸蛋白65在体内病毒复制中的作用
  • 批准号:
    7561989
  • 财政年份:
    2007
  • 资助金额:
    $ 76.76万
  • 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:
    $ 76.76万
  • 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:
    $ 76.76万
  • 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:
    $ 76.76万
  • 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:
    $ 76.76万
  • 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:
    $ 76.76万
  • 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:
    $ 76.76万
  • 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:
    $ 76.76万
  • 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:
    $ 76.76万
  • 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:
    $ 76.76万
  • 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:
    $ 76.76万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了