Group A Streptococcus Vaccination to prevent Strep throat in an NHP model
A 组链球菌疫苗接种可预防 NHP 模型中的链球菌性咽喉炎
基本信息
- 批准号:10507934
- 负责人:
- 金额:$ 35.37万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-16 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAntibodiesAntibody AffinityAutoimmuneAutoimmune DiseasesB-LymphocytesBindingBiological AssayCD4 Positive T LymphocytesCellular AssayChildChildhoodClinicalCollaborationsCytotoxic T-LymphocytesDataDevelopmentDiseaseEtiologyFundingGoalsHeart ValvesHelper-Inducer T-LymphocyteHumanImmuneImmune responseImmunoglobulin GInfectionKnowledgeLeadLeftLymphoid TissueMacaca mulattaMeasuresMediatingMemory B-LymphocyteModelingMolecular MimicryMusNamesNaturePersonsPharyngeal structurePharyngitisPhosphoserinePlayPrimatesProcessProteinsRecurrenceResearchResourcesRheumatic FeverRheumatic Heart DiseaseRiskRoleStreptococcal InfectionsStreptococcal VaccinesStreptococcus pyogenesStructure of germinal center of lymph nodeSuperantigensT-Cell ReceptorT-LymphocyteTonsilTonsillectomyTonsillitisToxic Shock SyndromeToxoidsUnited States National Institutes of HealthUp-RegulationVaccinatedVaccinationVaccinesVirulence FactorsWorld Health Organizationacquired immunityadaptive immune responsealuminum sulfateantigen-specific T cellsclinical developmentcohortcross reactivityerythrogenic toxinexperimental studyheart damagehumanized mouseimmunogenicityin vivomouse modelnonhuman primatepreventrecurrent infectionresponsevaccination outcome
项目摘要
Project Summary:
There are currently no approved vaccines for Group A Streptococcus (GAS). GAS is a widespread
pediatric problem causing an estimated 616 million cases of strep throat each year worldwide. Untreated strep
throat can lead to serious autoimmune sequelae such as rheumatic heart disease (RHD) which inadvertently
develops out of molecular mimicry from the host immune response to GAS infection. RHD results from damaged
heart valves, claiming the lives of 288,000 people each year worldwide, per the World Health Organization.
Therefore there is a critical need for a GAS vaccine.
We had first studied why some children get recurrent strep throat by studying the tonsillar germinal center
response in children who had undergone tonsillectomy for either recurrent strep tonsillitis or non-recurrent
tonsillitis. Tonsils are the lymphoid tissue which likely mount the first adaptive immune response to GAS. We
observed that children with recurrent strep throat had a deficit in circulating antibodies against a critical GAS
virulence factor streptococcus pyrogenic exotoxin A (SpeA). This was an interesting finding as there has been a
long clinical association demonstrating the protective nature of SpeA antibodies against the development of GAS
toxic shock syndrome. SpeA is a superantigen which is necessary to establish infection in a humanized mouse
model. We discovered that SpeA induced CD4+ T cells with the capacity to kill instead of help B cells within
germinal centers. We named these cells “killer T follicular helper (Tfh)” cells. We found that children with recurrent
strep throat had more SpeA induced “killer Tfh” cells and significantly smaller germinal centers, likely explaining
their propensity for recurrent strep infections. We hypothesize that an SpeA toxoid vaccination will protect against
GAS pharyngitis or tonsillitis by limiting the development of SpeA-induced “killer Tfh” cells and allowing for the
development of GAS-specific germinal center responses to quickly clear a GAS tonsillar infection. This proposal
focuses on evaluating whether an SpeA toxoid vaccine will prevent GAS tonsillitis and pharyngitis in a non-
human primate model and understanding the impact of SpeA toxoid vaccination in altering the GAS germinal
center response. The long term objective is to demonstrate the utility of GAS toxoid vaccinations in preventing
disease.
项目摘要:
目前还没有A组链球菌(GAS)的批准疫苗。GAS是一种广泛的
儿科问题,每年在全世界造成估计6.16亿例链球菌性咽喉炎。未经治疗的链球菌
咽喉可能导致严重的自身免疫后遗症,如风湿性心脏病(RHD),
从宿主对GAS感染的免疫反应的分子模拟中发展出来。RHD是由损坏的
据世界卫生组织统计,心脏瓣膜每年夺去全球28.8万人的生命。
因此,迫切需要一种GAS疫苗。
我们首先通过研究扁桃体生发中心来研究为什么有些孩子会复发链球菌性咽喉炎
因复发性或非复发性链球菌扁桃体炎接受扁桃体切除术的儿童的反应
扁桃体炎扁桃体是淋巴组织,可能对GAS产生第一个适应性免疫应答。我们
观察到患有复发性链球菌性咽喉炎的儿童缺乏针对关键GAS的循环抗体,
毒力因子链球菌致热外毒素A(SpeA)。这是一个有趣的发现,
长期的临床关联证明SpeA抗体对GAS发展的保护性
中毒性休克综合征SpeA是在人源化小鼠中建立感染所必需的超抗原
模型我们发现SpeA诱导的CD4+ T细胞具有杀死体内B细胞的能力,
老年中心我们将这些细胞命名为“杀伤性T滤泡辅助(Tfh)”细胞。我们发现,
链球菌咽喉炎有更多的SpeA诱导的“杀手Tfh”细胞和明显较小的生发中心,这可能解释了
他们反复感染链球菌的倾向我们假设SpeA类毒素疫苗可以预防
通过限制SpeA诱导的“杀伤Tfh”细胞的发展,
GAS特异性生发中心反应的发展,以快速清除GAS扁桃体感染。这项建议
重点是评估SpeA类毒素疫苗是否能预防非GAS患者的GAS扁桃体炎和咽炎。
人类灵长类动物模型和理解SpeA类毒素疫苗接种在改变GAS基因中的影响
中心响应长期目标是证明GAS类毒素疫苗在预防
疾病
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 }}
Jennifer Marie Dan其他文献
Jennifer Marie Dan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('Jennifer Marie Dan', 18)}}的其他基金
Group A Streptococcus Vaccination to prevent Strep throat in an NHP model
A 组链球菌疫苗接种可预防 NHP 模型中的链球菌性咽喉炎
- 批准号:
10647875 - 财政年份:2022
- 资助金额:
$ 35.37万 - 项目类别:
The Immunology of Recurrent Group A Streptococcus Tonsillitis
复发性 A 族链球菌扁桃体炎的免疫学
- 批准号:
10025784 - 财政年份:2018
- 资助金额:
$ 35.37万 - 项目类别:
The Immunology of Recurrent Group A Streptococcus Tonsillitis
复发性 A 族链球菌扁桃体炎的免疫学
- 批准号:
10395592 - 财政年份:2018
- 资助金额:
$ 35.37万 - 项目类别:
The Immunology of Recurrent Group A Streptococcus Tonsillitis
复发性 A 族链球菌扁桃体炎的免疫学
- 批准号:
9905482 - 财政年份:2018
- 资助金额:
$ 35.37万 - 项目类别:
相似海外基金
University of Aberdeen and Vertebrate Antibodies Limited KTP 23_24 R1
阿伯丁大学和脊椎动物抗体有限公司 KTP 23_24 R1
- 批准号:
10073243 - 财政年份:2024
- 资助金额:
$ 35.37万 - 项目类别:
Knowledge Transfer Partnership
Role of Natural Antibodies and B1 cells in Fibroproliferative Lung Disease
天然抗体和 B1 细胞在纤维增生性肺病中的作用
- 批准号:
10752129 - 财政年份:2024
- 资助金额:
$ 35.37万 - 项目类别:
CAREER: Next-generation protease inhibitor discovery with chemically diversified antibodies
职业:利用化学多样化的抗体发现下一代蛋白酶抑制剂
- 批准号:
2339201 - 财政年份:2024
- 资助金额:
$ 35.37万 - 项目类别:
Continuing Grant
Isolation and characterisation of monoclonal antibodies for the treatment or prevention of antibiotic resistant Acinetobacter baumannii infections
用于治疗或预防抗生素耐药鲍曼不动杆菌感染的单克隆抗体的分离和表征
- 批准号:
MR/Y008693/1 - 财政年份:2024
- 资助金额:
$ 35.37万 - 项目类别:
Research Grant
Developing first-in-class aggregation-specific antibodies for a severe genetic neurological disease
开发针对严重遗传神经系统疾病的一流聚集特异性抗体
- 批准号:
10076445 - 财政年份:2023
- 资助金额:
$ 35.37万 - 项目类别:
Grant for R&D
Discovery of novel nodal antibodies in the central nervous system demyelinating diseases and elucidation of the mechanisms through an optic nerve demyelination model
发现中枢神经系统脱髓鞘疾病中的新型节点抗体并通过视神经脱髓鞘模型阐明其机制
- 批准号:
23K14783 - 财政年份:2023
- 资助金额:
$ 35.37万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of the mechanisms controlling the physicochemical properties and functions of supercharged antibodies and development of their applications
阐明控制超电荷抗体的理化性质和功能的机制及其应用开发
- 批准号:
23KJ0394 - 财政年份:2023
- 资助金额:
$ 35.37万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Role of antibodies in hepatitis E virus infection
抗体在戊型肝炎病毒感染中的作用
- 批准号:
10639161 - 财政年份:2023
- 资助金额:
$ 35.37万 - 项目类别:
Defining the protective or pathologic role of antibodies in Post-Ebola Syndrome
定义抗体在埃博拉后综合症中的保护或病理作用
- 批准号:
10752441 - 财政年份:2023
- 资助金额:
$ 35.37万 - 项目类别:
Human CMV monoclonal antibodies as therapeutics to inhibit virus infection and dissemination
人 CMV 单克隆抗体作为抑制病毒感染和传播的治疗药物
- 批准号:
10867639 - 财政年份:2023
- 资助金额:
$ 35.37万 - 项目类别: