Specific T and B cell responses to candidate Treponema pallidum outer membrane protein vaccine antigens
对候选梅毒螺旋体外膜蛋白疫苗抗原的特异性 T 和 B 细胞反应
基本信息
- 批准号:10671517
- 负责人:
- 金额:$ 63.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AdjuvantAffinityAftercareAnimal ModelAnti-Bacterial AgentsAntibodiesAntibody ResponseAntigensB-LymphocytesBindingBiological AssayBloodCD4 Positive T LymphocytesCell AdhesionCellsCellular ImmunityClinical TrialsComplexEndothelial CellsEpitopesEvaluationExhibitsFamilyGlobus PallidusGoalsHelper-Inducer T-LymphocyteHumanImmuneImmune responseImmunityImmunizationIndividualInfectionIngestionInterferon Type IIKnowledgeLeadLengthLesionMacrophageMediatingMembrane ProteinsMemoryMemory B-LymphocyteModelingMonoclonal AntibodiesMusN-terminalOrganismOryctolagus cuniculusPatientsPeripheral Blood Mononuclear CellPersonsPositioning AttributePrevalencePreventive vaccineProcessProductionResearchResolutionSeriesSerumSexually Transmitted DiseasesSiteSkinStructureSyphilisSyphilitic chancreSystemT cell responseT-LymphocyteTechnologyTestingTh1 CellsTissuesTreponema pallidumUniversitiesVaccinatedVaccinationVaccine AntigenWashingtonWorkcandidate identificationcell motilitycytokinedesignfirst-in-humanimmunogenicimmunogenicityimprovedmembermemory CD4 T lymphocyteresponseseropositiveskin lesionsynergismsyphilis vaccinetissue resident memory T cellvaccine candidatevaccinology
项目摘要
ABSTRACT
Syphilis is a devastating human infection caused by Treponoma pallidum (Tp). Within this overall STI CRC
application entitled “Syphilis vaccine to protect against local and disseminated T. pallidum infection”, this
Project concerns the CD4 T cell and antibody response to Tp Vaccine Candidate Antigens (TpVCA) identified
by Project 1 and Project 2 Leaders. These include Tp0751, an outer membrane protein involved in endothelial
cell adhesion, and members of the Tpr family. Collectively, our research team has shown using the rabbit
model of Tp vaccination and infection that vaccination with these TpVCA leads to significant, partial protection
against challenge. Protection is thought to be antibody mediated. In turn, antibody responses are dependent
on CD4 T cell help from T follicular helper (TFH) cells. The TH1 CD4 T cell response also assists Tp-specific
antibody by secreting interferon-gamma to activate macrophages to phagocytose Tp organisms coated by
specific antibody. The premise of Project 3 is that a detailed understanding of the acquired immune response
to TpVCA will assist a reiterative process by which Projects 1 and 2 will be able to improve TpVCA design,
Project 3 contains three Aims. In Aim 1, state-of-the-art single B cell technology will be used to isolate naïve
and memory rabbit and human B cells that produce TpVCA-specific monoclonal antibodies (mAb). These
mAbs will be studied in functional assays by Projects 1 and 2 for anti-Tp functional activities such as
opsonophagocytosis and Tp neutralization in infection challenge models. The epitopes recognized by the most
potent mAbs will be determined, and the crystal structures of mAb-TpVCA complexes determined if possible,
to uncover the TpVCA domains that bear functional anti-bacterial epitopes. Aim 2 will rank the TpVCA for
prevalence and levels of CD4 TFH and TH1 cells in the blood of persons with symptomatic and asymptomatic
Tp infection, and explore whether Tp-specific CD4 T-cells migrate to sites of infection or are retained as tissue
resident memory T cells. Aim 3 will test the best candidate TpVCA from Projects 1 and 2, with a series of
proprietary adjuvants that are suitable for use in humans, in mouse humoral and CD4 immunogenicity assays.
During the STI CRC period, Project 3 will critically synergize with the other Projects and Cores to downselect
and optimize antigen and adjuvants with the goal of delivering a lead Tp vaccine candidate suitable for
advancement to first in human clinical trials.
摘要
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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David M Koelle其他文献
David M Koelle的其他文献
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{{ truncateString('David M Koelle', 18)}}的其他基金
C19 SARS-CoV-2-specific T cells in the infected nasel epithelium
受感染鼻上皮中的 C19 SARS-CoV-2 特异性 T 细胞
- 批准号:
10285229 - 财政年份:2021
- 资助金额:
$ 63.87万 - 项目类别:
C19 SARS-CoV-2-specific T cells in the infected nasel epithelium
受感染鼻上皮中的 C19 SARS-CoV-2 特异性 T 细胞
- 批准号:
10430281 - 财政年份:2021
- 资助金额:
$ 63.87万 - 项目类别:
Project 3: Adaptive immunity to MCPyV in Merkel cell carcinoma
项目3:默克尔细胞癌中MCPyV的适应性免疫
- 批准号:
10380819 - 财政年份:2019
- 资助金额:
$ 63.87万 - 项目类别:
Project 3: Adaptive immunity to MCPyV in Merkel cell carcinoma
项目3:默克尔细胞癌中MCPyV的适应性免疫
- 批准号:
10629192 - 财政年份:2019
- 资助金额:
$ 63.87万 - 项目类别:
Cutaneous pathogen-specific tissue resident memory T cells in human aging
人类衰老过程中皮肤病原体特异性组织常驻记忆 T 细胞
- 批准号:
10624283 - 财政年份:2019
- 资助金额:
$ 63.87万 - 项目类别:
Cutaneous pathogen-specific tissue resident memory T cells in human aging
人类衰老过程中皮肤病原体特异性组织常驻记忆 T 细胞
- 批准号:
10186853 - 财政年份:2019
- 资助金额:
$ 63.87万 - 项目类别:
Cutaneous pathogen-specific tissue resident memory T cells in human aging
人类衰老过程中皮肤病原体特异性组织常驻记忆 T 细胞
- 批准号:
9923517 - 财政年份:2019
- 资助金额:
$ 63.87万 - 项目类别:
Cutaneous pathogen-specific tissue resident memory T cells in human aging
人类衰老过程中皮肤病原体特异性组织常驻记忆 T 细胞
- 批准号:
10228544 - 财政年份:2019
- 资助金额:
$ 63.87万 - 项目类别:
Specific T and B cell responses to candidate Treponema pallidum outer membrane protein vaccine antigens
对候选梅毒螺旋体外膜蛋白疫苗抗原的特异性 T 和 B 细胞反应
- 批准号:
10219125 - 财政年份:2019
- 资助金额:
$ 63.87万 - 项目类别:
Cutaneous pathogen-specific tissue resident memory T cells in human aging
人类衰老过程中皮肤病原体特异性组织常驻记忆 T 细胞
- 批准号:
10468080 - 财政年份:2019
- 资助金额:
$ 63.87万 - 项目类别:
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