Early in vivo Expressed Antigens and their Role in Virulence, Immune Response, and Vaccines for Coccidioidomycosis
早期体内表达的抗原及其在球孢子菌病毒力、免疫反应和疫苗中的作用
基本信息
- 批准号:10689662
- 负责人:
- 金额:$ 154.27万
- 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:2022-08-24 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:Animal ModelAnimalsAntibodiesAntigensBasic ScienceCRISPR/Cas technologyClinicalClinical TrialsCoccidioidesCoccidioides immitisCoccidioides posadasiiCoccidioidomycosisCommunitiesComplexDNADNA VaccinesDNA sequencingDataDevelopmentDiagnosticDiagnostic testsDiseaseEpitopesGene ExpressionGene Expression ProfileGenesGoalsHumanImmuneImmune responseImmunizationInfectionInfrastructureInsectaInstitutionKnock-outKnowledgeLinkLipidsLocationMacaca nemestrinaMessenger RNAModalityModelingMorbidity - disease rateMusNucleic Acid Amplification TestsNucleic Acid VaccinesNucleic AcidsPathogenesisPatientsPatternPeptidesPopulationPreventionProcessProtein SecretionProteinsRNARNA replicationRNA vaccinationRNA vaccineResearchResearch PersonnelResearch Project GrantsRoleSerology testT cell responseT-Cell ReceptorT-LymphocyteT-cell receptor repertoireTechnologyTestingTherapeuticTherapeutic AgentsTimeTranslational ResearchUnited StatesVaccinationVaccine AntigenVaccine DesignVaccinesVertebratesVirulenceVirulence FactorsWaxesWorkclinical research sitecompanion diagnosticsdesert feverdesigndiagnostic signaturediagnostic strategydiagnostic tooldisease diagnosisgene gungene producthuman diseasein vivoinsightknockout genelongitudinal analysismortalitymouse modelnano-stringnanoGoldnanoparticlenonhuman primatenovelnovel diagnosticsnovel vaccinespathogenpreventrespiratoryresponsescreeningserological markertherapeutic evaluationtooltranscriptome sequencingvaccine candidatevaccine developmentvaccine evaluationvirulence gene
项目摘要
OVERALL Section
Title: Early in vivo expressed antigens and their role in virulence, immune response, and vaccines for
coccidioidomycosis.
SUMMARY
Coccidioidomycosis, also known as Valley Fever (VF), is an important fungal disease caused by two different
Coccidioides species that results in regionally important mortality and even greater morbidity. We have
assembled a team to define the changes that occur in human and animal immune responses to VF, and to use
this knowledge for designing new vaccines and diagnostic tests. This work will capitalize upon our detailed
observations of Coccidioides gene expression patterns during the earliest stages of infections. We hypothesize
that some Coccidioides early genes are virulence factors and critical for causing disease. Research Project 1
will test their role through gene knockouts using CRISPR-Cas9 technology and virulence testing in wax worm
(Galleria) and mouse VF models. Critical virulence factors will become diagnostic and vaccine targets. In addition
to the wax worm and mouse models, we develop a non-human primate (pig-tailed macaques) that will more
closely resemble VF in humans. In humans and vertebrate animal models, the role of T cells cannot be
overemphasized and Research Project 2 will use focused deep DNA sequencing to identify classes of T cell
receptors (TCR) that develop in response to early expressed Coccidioides genes. We will generate TCR
sequences from patients at three clinical locations that span the endemic zones for the pathogen. The TCR
repertoire from patients will be used to identify novel diagnostic signatures (e.g., public TCRs) and, also, help
identify immune responses to key antigens that can be targeted for vaccine development. Hence, both TCR and
early virulence genes represent excellent candidates for vaccine design that will be explored in Research
Project 3 using nucleic acid (NA) based vaccines (RNA and DNA) that can rapidly test a large panel of antigens
through the immunization of mice against infection. The DNA vaccine will be based upon delivery on gold
nanoparticles and Gene Gun, while the mRNA employs self-replicating RNA molecules (repRNA) and a Lipid
InOrganic Nanoparticle (LION). Both are proven technologies that are moving forward into clinical trials for other
diseases. Our goal in the NA vaccine mouse studies is to identify the best antigens and delivery modality for
vaccine testing in the NHP model and to define their immune mechanisms of protection. This work is only
possible through the integrated efforts of investigators at seven different institutions, including three clinical sites,
as no single institution has the requisite breadth of expertise and infrastructure. While we will generate
fundamental knowledge about Coccidioides and VF, we will also make translational advances towards
preventing and diagnosing the disease.
整体部分
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)
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Paul Stephen Keim其他文献
Paul Stephen Keim的其他文献
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{{ truncateString('Paul Stephen Keim', 18)}}的其他基金
Early in vivo expressed antigens and their role in virulence, immune response, and vaccines for coccidioidomycosis
早期体内表达的抗原及其在球孢子菌病毒力、免疫反应和疫苗中的作用
- 批准号:
10689664 - 财政年份:2022
- 资助金额:
$ 154.27万 - 项目类别:
Early in vivo expressed antigens and their role in virulence, immune response, and vaccines for coccidioidomycosis
早期体内表达的抗原及其在球孢子菌病毒力、免疫反应和疫苗中的作用
- 批准号:
10356626 - 财政年份:2022
- 资助金额:
$ 154.27万 - 项目类别:
Early in vivo Expressed Antigens and their Role in Virulence, Immune Response, and Vaccines for Coccidioidomycosis
早期体内表达的抗原及其在球孢子菌病毒力、免疫反应和疫苗中的作用
- 批准号:
10356625 - 财政年份:2022
- 资助金额:
$ 154.27万 - 项目类别:
Early in vivo Expressed Antigens and their Role in Virulence, Immune Response, and Vaccines for Coccidioidomycosis
早期体内表达的抗原及其在球孢子菌病毒力、免疫反应和疫苗中的作用
- 批准号:
10891793 - 财政年份:2022
- 资助金额:
$ 154.27万 - 项目类别:
Functional genomic analyses of emerging Cryptococcus subtypes in North America
北美新兴隐球菌亚型的功能基因组分析
- 批准号:
8386240 - 财政年份:2012
- 资助金额:
$ 154.27万 - 项目类别:
Functional genomic analyses of emerging Cryptococcus subtypes in North America
北美新兴隐球菌亚型的功能基因组分析
- 批准号:
8505370 - 财政年份:2012
- 资助金额:
$ 154.27万 - 项目类别:
Genomic Correlates with Differential Virulence in Melioidosis Animal Models
类鼻疽动物模型中基因组与差异毒力的相关性
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8260261 - 财政年份:2011
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Molecular Antibiotic Resistance Arrays for clinical microbiology laboratories
用于临床微生物学实验室的分子抗生素耐药性芯片
- 批准号:
8281561 - 财政年份:2010
- 资助金额:
$ 154.27万 - 项目类别:
Molecular Antibiotic Resistance Arrays for clinical microbiology laboratories
用于临床微生物学实验室的分子抗生素耐药性芯片
- 批准号:
8477122 - 财政年份:2010
- 资助金额:
$ 154.27万 - 项目类别:
Molecular Antibiotic Resistance Arrays for clinical microbiology laboratories
用于临床微生物学实验室的分子抗生素耐药性芯片
- 批准号:
8088115 - 财政年份:2010
- 资助金额:
$ 154.27万 - 项目类别:
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