Identifying the Breadth of Antibody Responses to Clostridioides difficile Infection
确定抗体对艰难梭菌感染反应的广度
基本信息
- 批准号:10186695
- 负责人:
- 金额:$ 7.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-09 至 2022-05-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAnimal ModelAnimalsAntibodiesAntibody ResponseAntigen TargetingAntigensCellsCenters for Disease Control and Prevention (U.S.)ChildChildhoodClinicalClostridium difficileColitisCommunicable DiseasesDataDatabasesDevelopmentDiarrheaEnvironmentEnzyme-Linked Immunosorbent AssayEpitopesFDA approvedFeasibility StudiesFutureGenesGenomeGenomicsGoalsHealth ExpendituresHumanImmuneImmune responseImmunizationImmunocompetentImmunoglobulinsImmunologicsImmunotherapyIn VitroIndividualInfectionInfection preventionInvestigationKnowledgeLifeLightLinkMethodsMicrobiologyMolecular EpidemiologyMonoclonal AntibodiesMorbidity - disease rateMucocutaneous Lymph Node SyndromePathogenesisPatientsPediatric HospitalsPlasma CellsPlasmablastPrevention strategyPreventive therapyProtein FragmentProteinsProteomeProteomicsPublic HealthRecurrenceResearchResourcesReverse Transcriptase Polymerase Chain ReactionRiskTestingToxinTransfectionTransgenic MiceTranslatingUniversitiesVaccinationVaccine AntigenVaccinesVibrio choleraeVibrio cholerae infectionWorkbasecareer developmentclinical developmentclinical epidemiologyclinical investigationcohortdesigndiarrheal diseaseexpression vectorhealthcare-associated infectionshuman monoclonal antibodiesimmunogenicimmunogenicityimprovedinnovationmortalitynovelpathogenperipheral bloodpreclinical studypreventpublic health relevancerecurrent infectionresponseskillssynthetic antibodiestandem mass spectrometrytherapeutically effectivetransmission processwhole genome
项目摘要
PROJECT SUMMARY ABSTRACT
Clostridioides (Clostridium) difficile infection (CDI) is a common healthcare-associated infection in US children
and adults. CDI, which ranges from mild diarrhea to life-threatening colitis, is associated with substantial
morbidity, mortality, and excess healthcare expenditures. The CDC has classified C. difficile as an “immediate
public health threat that requires urgent and aggressive action.” This call to action has expanded CDI
investigation and prompted efforts to develop novel and more effective prevention strategies. Immunological
agents are a promising strategy for CDI prevention; a monoclonal antibody against C. difficile is recently FDA
approved for CDI prevention, and several toxin-based vaccines are in clinical development. Despite these
products showing promise for CDI prevention, many patients have failed these therapies. The immunizations
currently under clinical investigation were developed based on knowledge of C. difficile immunogenicity in
animals, which may not adequately represent C. difficile immunogenicity in humans. To better understand the
relative immunogenicity of C. difficile antigens in humans, we propose characterization of the plasmablast
response following natural CDI. Plasmablasts are plasma cell precursors that produce antibodies directed
against a pathogen; antigen-specific plasmablasts can be isolated from peripheral blood 1-3 weeks after
infection. Antibodies encoded by these cells can be produced in vitro and the target antigens identified. This
innovative method has been recently successfully applied to other infectious diseases, including to Kawasaki
Disease by our research team. By analyzing the plasmablast response following CDI, we will identify the
breadth of the human antibody response to C. difficile infection. We hypothesize that the antibody response to
C. difficile is not limited to toxin antigens, and that antibodies against both toxin and non-toxin antigens provide
protection against CDI. Specifically, in this feasibility study, we aim to identify and clone the peripheral blood
plasmablast response following CDI in 3 children and 3 adults, and identify C. difficile antigenic targets of
oligoclonal post-CDI plasmablasts using various proteomics analyses. Knowledge gained in this feasibility
study will inform design of larger studies to validate immunogenicity of C. difficile antigens in a more diverse
patient cohort and the neutralizing ability of these antibodies across a diverse set of C. difficile strain types. In
future studies, we will determine the specific toxin and non-toxin epitopes recognized by antibodies following
natural CDI in humans, and we will study how antibody responses to C. difficile toxin and non-toxin antigens
impact C. difficile colonization and infection. Identification of broadly immunogenic antigens will guide future
work to investigate potential immunization candidates to prevent CDI and colonization. Our research team and
the Northwestern University academic environment possess the skills and resources, respectively, that are
necessary for successful completion of the proposed studies, including assembly of patient cohort, bacterial
genomics, plasmablast isolation, plasmablast antibody synthesis, and proteomics.
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项目摘要
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Translational Aspects of the Immunology of Clostridioides difficile Infection: Implications for Pediatric Populations.
艰难梭菌感染免疫学的转化方面:对儿童群体的影响。
- DOI:10.1093/jpids/piab089
- 发表时间:2021
- 期刊:
- 影响因子:3.2
- 作者:Kociolek,LarryK;Zackular,JosephP;Savidge,Tor
- 通讯作者:Savidge,Tor
Fidaxomicin for the treatment of Clostridioides difficile in children.
Fidaxomicin 用于治疗儿童艰难梭菌。
- DOI:10.2217/fmb-2020-0104
- 发表时间:2020
- 期刊:
- 影响因子:3.1
- 作者:Skinner,AndrewM;Scardina,Tonya;Kociolek,LarryK
- 通讯作者:Kociolek,LarryK
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{{ truncateString('LARRY K KOCIOLEK', 18)}}的其他基金
Identification of the antigenic targets of the clonal antibody response to Clostridioides difficile infection
鉴定针对艰难梭菌感染的克隆抗体反应的抗原靶点
- 批准号:
10742376 - 财政年份:2023
- 资助金额:
$ 7.84万 - 项目类别:
Optimizing the diagnosis of pediatric Clostridium difficile infection
优化儿科艰难梭菌感染的诊断
- 批准号:
9087683 - 财政年份:2016
- 资助金额:
$ 7.84万 - 项目类别:
Optimizing the diagnosis of pediatric Clostridium difficile infection
优化儿科艰难梭菌感染的诊断
- 批准号:
9220710 - 财政年份:2016
- 资助金额:
$ 7.84万 - 项目类别:
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