Development of a Vaccine for Staphylococcal Infections
葡萄球菌感染疫苗的开发
基本信息
- 批准号:10255984
- 负责人:
- 金额:$ 25.78万
- 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:2021-04-16 至 2021-11-30
- 项目状态:已结题
- 来源:
- 关键词:AbscessAddressAnaphylaxisAnimalsAntibiotic ResistanceAntibiotic TherapyAntibioticsAntibodiesAntibody-mediated protectionB-Cell Antigen ReceptorB-LymphocytesBacteremiaBacteriaBindingBiologicalBiological AssayBlood CirculationCathetersCaviaCell DegranulationCell secretionCellsChicagoChildhoodClinicalCommunitiesCommunity HospitalsCyclic GMPDetectionDevelopmentDevicesDiseaseDisease OutcomeEndotoxinsEscherichia coliExhibitsFc domainFutureGenerationsGenus staphylococcusGoalsHealthHistamine ReleaseHospitalizationHospitalsHumanImmuneImmune EvasionImmune responseImmunityImmunizationImmunoblottingImmunoglobulin GImmunoglobulin IdiotypesImmunoglobulin MImmunoglobulinsImmunotherapeutic agentImmunotherapyIndividualInfectionLeadLesionLung infectionsMediatingMembrane ProteinsMolecularMusNatural ImmunityNosocomial InfectionsOperative Surgical ProceduresOutcomeOutpatientsPaste substancePatientsPhasePopulationPrevalencePreventivePreventive vaccineProcessProductionPropertyProteinsPublic HealthRecurrenceResearchResidual stateResistanceRiskRisk FactorsSafetySalesSepsisSkin TissueSmall Business Technology Transfer ResearchSoft Tissue InfectionsStaphylococcal InfectionsStaphylococcal Protein AStaphylococcus aureusStaphylococcus aureus infectionStructure of mucous membrane of noseSuperantigensSurfaceSurgical Wound InfectionTestingTimeTreatment EfficacyUnited StatesUnited States Food and Drug AdministrationUniversitiesVaccinatedVaccine DesignVaccinesVariantVisitWorkadaptive immune responsecell bankclinical efficacyclinically significantcommercial applicationcostcrosslinkdesignefficacy testingimprovedimproved outcomemast cellmethicillin resistant Staphylococcus aureusmortalitymouse modelneutralizing antibodynovel therapeuticspathogenpreclinical developmentpreclinical efficacypreclinical safetypreventprogramspublic health relevancereceptorrecurrent infectionresponsesafety studysafety testingskeletalsoft tissuetherapeutic vaccinevaccine candidatevaccine developmentvaccine-induced immunityventilator-associated pneumoniavirtual
项目摘要
Project Summary / abstract:
Staphylococcus aureus causes skin and soft tissue infections (SSTI) that result in 14.2 million outpatient visits
per year and 850,000 hospital admissions. S. aureus infection is not associated with the development of
immunity and, even with surgical and antibiotic therapy, recurrent infections occur frequently. Infections with
antibiotic-resistant S. aureus strains, designated MRSA (methicillin-resistant S. aureus) are associated with
poor disease outcomes and are now identified in 22% of hospital isolates. In order to address the public health
crisis of MRSA, we are developing a vaccine to prevent invasive S. aureus infections. Key features of S.
aureus disease are the pathogen’s resistance to opsonophagocytic killing (OPK) and the suppression of the
host’s adaptive immune responses. Staphylococcal binding to immunoglobulin (Ig) is mediated by
staphylococcal protein A (SpA), a surface protein that associates with the Fc-domain of IgG and the heavy
chain of VH3 clan IgG and IgM. While the former activity provides protection from antibodies that induce OPK,
the latter, through the crosslinking of IgM receptors, triggers proliferation and B cells and secretion of non-
protective VH3 antibodies, thereby disrupting adaptive immune responses and the development of protective
immunity. We have developed SpA*, a vaccine that elicits SpA-neutralizing antibodies that effectively promote
OPK of the pathogen while also allowing the host to generate many different pathogen specific antibodies that
together eliminate S. aureus colonization and reduce the risk of invasive disease. This phase I STTR proposal
aims to establish the feasibility of generating the SpA* vaccine by establishing its preclinical safety and
biological efficacy.
项目摘要/摘要:
金黄色葡萄球菌导致皮肤和软组织感染(SSTI),导致1420万门诊就诊
每年有850,000人入院。金黄色葡萄球菌感染与该病的发生无关
而且,即使使用外科手术和抗生素治疗,反复感染也经常发生。感染:
耐药金黄色葡萄球菌菌株,命名为MRSA(耐甲氧西林金黄色葡萄球菌)与
疾病结局不佳,目前已在22%的医院分离株中发现。为了解决公共卫生问题
为了应对MRSA危机,我们正在开发一种疫苗,以防止金黄色葡萄球菌的侵袭性感染。S。
金黄色葡萄球菌病是病原体对吞噬细胞杀伤(OPK)的抵抗力和对
宿主的适应性免疫反应。葡萄球菌与免疫球蛋白(Ig)的结合是由
葡萄球菌蛋白A(SpA),一种与免疫球蛋白Fc结构域和重链相关的表面蛋白
VH3家族免疫球蛋白和免疫球蛋白M链。虽然前者的活性提供了对诱导OPK的抗体的保护,
后者通过IgM受体的交联,触发B细胞的增殖和分泌非
保护性VH3抗体,从而扰乱获得性免疫反应和保护性
豁免权。我们已经开发出SpA*,这是一种疫苗,可以诱导SpA中和抗体,有效地促进
OPK,同时也允许宿主产生许多不同的病原体特异性抗体,
共同消除金黄色葡萄球菌的定植,降低侵袭性疾病的风险。这项第一阶段的短期租约建议
旨在通过建立其临床前安全性和安全性来确定生产SpA*疫苗的可行性
生物功效。
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 }}
Dominique M. Missiakas其他文献
Dominique M. Missiakas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('Dominique M. Missiakas', 18)}}的其他基金
Biocontainment Research Support Service(s) Core
生物防护研究支持服务核心
- 批准号:
10793952 - 财政年份:2023
- 资助金额:
$ 25.78万 - 项目类别:
Optimal adjuvant/antigen formulation toward a Staphylococcus aureus human vaccine
金黄色葡萄球菌人疫苗的最佳佐剂/抗原配方
- 批准号:
10383513 - 财政年份:2022
- 资助金额:
$ 25.78万 - 项目类别:
Determinants of plague susceptibility and resistance
鼠疫易感性和抵抗力的决定因素
- 批准号:
10245980 - 财政年份:2020
- 资助金额:
$ 25.78万 - 项目类别:
Antibody therapy of MRSA colonization and infection
MRSA 定植和感染的抗体治疗
- 批准号:
10307576 - 财政年份:2019
- 资助金额:
$ 25.78万 - 项目类别:
Antibody therapy of MRSA colonization and infection
MRSA 定植和感染的抗体治疗
- 批准号:
10525253 - 财政年份:2019
- 资助金额:
$ 25.78万 - 项目类别:
Molecular basis and intervention of Staphylococcus aureus agglutination
金黄色葡萄球菌凝集的分子基础及干预
- 批准号:
8817809 - 财政年份:2014
- 资助金额:
$ 25.78万 - 项目类别:
Molecular basis and intervention of Staphylococcus aureus agglutination
金黄色葡萄球菌凝集的分子基础及干预
- 批准号:
8816265 - 财政年份:2014
- 资助金额:
$ 25.78万 - 项目类别:
Molecular basis and intervention of Staphylococcus aureus agglutination
金黄色葡萄球菌凝集的分子基础及干预
- 批准号:
9180674 - 财政年份:2014
- 资助金额:
$ 25.78万 - 项目类别:
Therapies of infections caused by gram-positive bacteria
革兰氏阳性菌引起的感染的治疗
- 批准号:
8448669 - 财政年份:2013
- 资助金额:
$ 25.78万 - 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:
$ 25.78万 - 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:
$ 25.78万 - 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:
$ 25.78万 - 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:
$ 25.78万 - 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:
$ 25.78万 - 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:
$ 25.78万 - 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:
$ 25.78万 - 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:
$ 25.78万 - 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:
$ 25.78万 - 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:
$ 25.78万 - 项目类别:
Research Grant