Activation of innate immune responses by a polyphosphazene adjuvant in pigs
聚磷腈佐剂激活猪的先天免疫反应
基本信息
- 批准号:RGPIN-2014-03981
- 负责人:
- 金额:$ 2.19万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2015
- 资助国家:加拿大
- 起止时间:2015-01-01 至 2016-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Adjuvants are substances which enhance immune responses to vaccines. To date, adjuvants have been used in billions of doses of vaccines for animals. Despite their extensive use, very little is known about how adjuvants work. This prompted one famous scientist to state that "adjuvants are the immunologist's dirty little secret". The lack of detailed understanding of how adjuvants work is a barrier to their rational use in vaccines. Furthermore, knowing how adjuvants work would alleviate some of the perceptions regarding their safety.
Available evidence suggests that most adjuvants, if not all, act by stimulating innate immunity which in turn directs the development of antigen-specific immunity (adaptive immunity). Numerous investigators have demonstrated that adjuvants influence various aspects of innate immunity including; the production of certain chemical mediators (cytokines and chemokines), recruitment of immune cells and the promotion of antigen transport to draining lymph nodes.
We have published extensively on the strong activity of a novel adjuvant, poly[di(sodiumcarboxylatoethylphenoxy)phosphazene] (PCEP), which is a synthetic biodegradable and water-soluble polyphosphazene polymer. We have shown that PCEP dramatically increases immune responses to a variety of experimental bacterial and viral vaccines. Most of these earlier studies were done in mice, but we have recently demonstrated that PCEP is a promising adjuvant in pigs, and we are currently exploring the potential of PCEP in improving swine influenza virus (SIV) vaccines for pigs in two other projects (see ongoing research support). However, no information is available on how PCEP works in pigs, which is a barrier to its rational use. Since most adjuvants act by stimulating innate immunity, we reasoned that investigating how PCEP activates innate immunity will provide valuable information on how this adjuvant works in pigs. In this regard, we propose to perform the following studies; 1): Assess the regulation of immune response genes induced by PCEP at the injection site, 2) Investigate the effect of PCEP on local and systemic cytokine and chemokine concentrations, 3)Identify the immune cells recruited at the injection site and in the draining lymph node, 4) Investigate activation of immune cells by PCEP in vitro, and 5) Assess whether retention of "antigen-adjuvant complex" (depot formation) at the injection site is required for adjuvant activity of PCEP.
Understanding how adjuvants work will provide valuable information on their rational use and also on their safety. Results from the proposed work will be a significant contribution to this end. In addition, the proposed studies will lay groundwork for similar studies with other adjuvants used in animal vaccines.
佐剂是增强对疫苗的免疫反应的物质。迄今为止,佐剂已用于数十亿剂动物疫苗。尽管它们被广泛使用,但人们对佐剂的工作原理知之甚少。这促使一位著名的科学家说:“佐剂是免疫学家肮脏的小秘密”。对佐剂如何起作用缺乏详细的了解是其在疫苗中合理使用的障碍。此外,了解佐剂的工作原理将减轻人们对其安全性的一些看法。
现有证据表明,大多数佐剂(如果不是全部的话)通过刺激先天免疫起作用,而先天免疫又指导抗原特异性免疫(适应性免疫)的发展。许多研究者已经证明,佐剂影响先天免疫的各个方面,包括:某些化学介质(细胞因子和趋化因子)的产生,免疫细胞的募集和抗原转运到引流淋巴结的促进。
我们已经发表了大量关于新型佐剂聚[二(羧基乙基苯氧基钠)磷腈](PCEP)的强活性的文章,PCEP是一种合成的可生物降解的水溶性聚磷腈聚合物。我们已经表明,PCEP显着增加对各种实验性细菌和病毒疫苗的免疫反应。这些早期的研究大多是在小鼠中进行的,但我们最近已经证明PCEP是一种很有前途的猪佐剂,我们目前正在探索PCEP在其他两个项目中改进猪流感病毒(SIV)疫苗的潜力。然而,没有关于PCEP如何在猪中起作用的信息,这是其合理使用的障碍。由于大多数佐剂通过刺激先天免疫起作用,因此我们推断,研究PCEP如何激活先天免疫将为这种佐剂如何在猪中起作用提供有价值的信息。在这方面,我们建议进行以下研究:(1):评估PCEP在注射部位诱导的免疫应答基因的调节,2)研究PCEP对局部和全身细胞因子和趋化因子浓度的影响,3)鉴定注射部位和引流淋巴结中募集的免疫细胞,4)研究PCEP在体外对免疫细胞的激活,和5)评估PCEP的佐剂活性是否需要在注射部位保留“抗原-佐剂复合物”(贮库形成)。
了解佐剂的工作原理将为合理使用及其安全性提供有价值的信息。拟议工作的成果将为此作出重大贡献。此外,拟议的研究将为动物疫苗中使用的其他佐剂的类似研究奠定基础。
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 }}
Mutwiri, George其他文献
All three classes of CpG ODNs up-regulate IP-10 gene in pigs
- DOI:
10.1016/j.rvsc.2009.10.003 - 发表时间:
2010-04-01 - 期刊:
- 影响因子:2.4
- 作者:
Dar, Arshud;Nichani, Anil;Mutwiri, George - 通讯作者:
Mutwiri, George
CpG Oligodeoxynucleotides Activate Innate Immune Response that Suppresses Infectious Bronchitis Virus Replication in Chicken Embryos
- DOI:
10.1637/8560-121808-reg.1 - 发表时间:
2009-06-01 - 期刊:
- 影响因子:1.4
- 作者:
Dar, Arshud;Potter, Andy;Mutwiri, George - 通讯作者:
Mutwiri, George
Poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) is a potent enhancer of mixed Th1/Th2 immune responses in mice immunized with influenza virus antigens
- DOI:
10.1016/j.vaccine.2006.10.011 - 发表时间:
2007-01-26 - 期刊:
- 影响因子:5.5
- 作者:
Mutwiri, George;Benjamin, Ponn;Babiuk, Lorne A. - 通讯作者:
Babiuk, Lorne A.
Novel Bregs down-regulate TLR9-induced cytokine responses in sheep Peyer's patches
- DOI:
10.1016/j.vetimm.2011.04.011 - 发表时间:
2012-07-15 - 期刊:
- 影响因子:1.8
- 作者:
Booth, Jayaum;Jimbo, Steve;Mutwiri, George - 通讯作者:
Mutwiri, George
Activation of adjuvant core response genes by the novel adjuvant PCEP
- DOI:
10.1016/j.molimm.2012.03.026 - 发表时间:
2012-07-01 - 期刊:
- 影响因子:3.6
- 作者:
Awate, Sunita;Wilson, Heather L.;Mutwiri, George - 通讯作者:
Mutwiri, George
Mutwiri, George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('Mutwiri, George', 18)}}的其他基金
Mechanisms of action of adjuvants in pigs
佐剂对猪的作用机制
- 批准号:
RGPIN-2019-05266 - 财政年份:2022
- 资助金额:
$ 2.19万 - 项目类别:
Discovery Grants Program - Individual
Mechanisms of action of adjuvants in pigs
佐剂对猪的作用机制
- 批准号:
RGPIN-2019-05266 - 财政年份:2021
- 资助金额:
$ 2.19万 - 项目类别:
Discovery Grants Program - Individual
Mechanisms of action of adjuvants in pigs
佐剂对猪的作用机制
- 批准号:
RGPIN-2019-05266 - 财政年份:2020
- 资助金额:
$ 2.19万 - 项目类别:
Discovery Grants Program - Individual
Mechanisms of action of adjuvants in pigs
佐剂对猪的作用机制
- 批准号:
RGPIN-2019-05266 - 财政年份:2019
- 资助金额:
$ 2.19万 - 项目类别:
Discovery Grants Program - Individual
Activation of innate immune responses by a polyphosphazene adjuvant in pigs
聚磷腈佐剂激活猪的先天免疫反应
- 批准号:
RGPIN-2014-03981 - 财政年份:2018
- 资助金额:
$ 2.19万 - 项目类别:
Discovery Grants Program - Individual
Activation of innate immune responses by a polyphosphazene adjuvant in pigs
聚磷腈佐剂激活猪的先天免疫反应
- 批准号:
RGPIN-2014-03981 - 财政年份:2017
- 资助金额:
$ 2.19万 - 项目类别:
Discovery Grants Program - Individual
Activation of innate immune responses by a polyphosphazene adjuvant in pigs
聚磷腈佐剂激活猪的先天免疫反应
- 批准号:
RGPIN-2014-03981 - 财政年份:2016
- 资助金额:
$ 2.19万 - 项目类别:
Discovery Grants Program - Individual
Activation of innate immune responses by a polyphosphazene adjuvant in pigs
聚磷腈佐剂激活猪的先天免疫反应
- 批准号:
RGPIN-2014-03981 - 财政年份:2014
- 资助金额:
$ 2.19万 - 项目类别:
Discovery Grants Program - Individual
Regulation of innate immune responses in the intestine
肠道先天免疫反应的调节
- 批准号:
227402-2009 - 财政年份:2013
- 资助金额:
$ 2.19万 - 项目类别:
Discovery Grants Program - Individual
Regulation of innate immune responses in the intestine
肠道先天免疫反应的调节
- 批准号:
227402-2009 - 财政年份:2012
- 资助金额:
$ 2.19万 - 项目类别:
Discovery Grants Program - Individual
相似国自然基金
盐皮质激素受体抑制2型固有淋巴细胞活化加重心肌梗死后心室重构的作用机制
- 批准号:82372202
- 批准年份:2023
- 资助金额:49.00 万元
- 项目类别:面上项目
Innate-likeB细胞受损介导凋亡细胞的清除障碍在系统性红斑狼疮发病中的作用及机制研究
- 批准号:81860295
- 批准年份:2018
- 资助金额:35.0 万元
- 项目类别:地区科学基金项目
控制肠道病毒71型感染的先天性免疫保护机制及其应用
- 批准号:31270951
- 批准年份:2012
- 资助金额:80.0 万元
- 项目类别:面上项目
C型凝集素样受体识别在原发性皮肤毛霉病中的作用
- 批准号:81171510
- 批准年份:2011
- 资助金额:58.0 万元
- 项目类别:面上项目
microRNA对机体抗病毒固有免疫应答RIG-I信号途径的调控作用及机制研究
- 批准号:31170826
- 批准年份:2011
- 资助金额:70.0 万元
- 项目类别:面上项目
干扰素刺激基因2',3'环核苷酸磷酸二酯酶(CNP)抗病毒特性的研究
- 批准号:31170853
- 批准年份:2011
- 资助金额:56.0 万元
- 项目类别:面上项目
转录因子IRF3的泛素和SUMO修饰调节机制及其在抗病毒天然免疫中的功能
- 批准号:31130020
- 批准年份:2011
- 资助金额:315.0 万元
- 项目类别:重点项目
细胞内受体TLR9、NOD1和NOD2在不可分型流感嗜血杆菌肺组织感染中的作用
- 批准号:30670929
- 批准年份:2006
- 资助金额:27.0 万元
- 项目类别:面上项目
相似海外基金
Targeting SHP-1 through a newfound metabolite-regulated cysteine activation site
通过新发现的代谢物调节的半胱氨酸激活位点靶向 SHP-1
- 批准号:
10802649 - 财政年份:2023
- 资助金额:
$ 2.19万 - 项目类别:
Layilin as a modulator of platelet activation and thromboinflammation
Layilin 作为血小板活化和血栓炎症调节剂
- 批准号:
10607168 - 财政年份:2023
- 资助金额:
$ 2.19万 - 项目类别:
Investigating whole-body innate immune activation in Alzheimer's disease using PET imaging and immune profiling
使用 PET 成像和免疫分析研究阿尔茨海默病的全身先天免疫激活
- 批准号:
10749393 - 财政年份:2023
- 资助金额:
$ 2.19万 - 项目类别:
Defining the role of persistent DNA bridges in tumor-intrinsic immune activation in hereditary breast and ovarian cancer
确定持久性 DNA 桥在遗传性乳腺癌和卵巢癌肿瘤内在免疫激活中的作用
- 批准号:
10606942 - 财政年份:2023
- 资助金额:
$ 2.19万 - 项目类别:
Innate immune receptor-mediated activation of adipose-derived stem cells against biofilm infections
先天免疫受体介导的脂肪干细胞激活以抵抗生物膜感染
- 批准号:
23K08672 - 财政年份:2023
- 资助金额:
$ 2.19万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Activation of sperm/uterine innate immune receptor TLR2 for high fertility after cow embryo transfer
激活精子/子宫先天免疫受体 TLR2 以提高奶牛胚胎移植后的高生育力
- 批准号:
22KF0018 - 财政年份:2023
- 资助金额:
$ 2.19万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Employing Humanized Microbiome Mice to Understand Immune Activation and Translational Therapeutic Potential in Glioblastoma
利用人源化微生物组小鼠来了解胶质母细胞瘤的免疫激活和转化治疗潜力
- 批准号:
10665439 - 财政年份:2023
- 资助金额:
$ 2.19万 - 项目类别:
Mast Cell Activation as a Common Mechanism of Pulmonary Toxicity by Chemical Threat Agents
肥大细胞激活是化学威胁剂肺部毒性的常见机制
- 批准号:
10887265 - 财政年份:2023
- 资助金额:
$ 2.19万 - 项目类别:
Signaling activation and constraints in maintaining immune homeostasis
维持免疫稳态的信号激活和限制
- 批准号:
10619849 - 财政年份:2023
- 资助金额:
$ 2.19万 - 项目类别:
Interferon regulation of gamma delta intraepithelial lymphocyte activation
干扰素调节γδ上皮内淋巴细胞活化
- 批准号:
10819812 - 财政年份:2023
- 资助金额:
$ 2.19万 - 项目类别: