Building the foundations of commensal vaccines
建立共生疫苗的基础
基本信息
- 批准号:10709507
- 负责人:
- 金额:$ 77.09万
- 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:2022-09-23 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:Acute Lymphocytic LeukemiaAdaptive Immune SystemAddressAdjuvantAntigensAreaAutoimmuneAutoimmune DiseasesAutoimmunityB-LymphocytesBacteriaBasic ScienceBiological ProductsBiomedical ResearchCD19 geneCD8-Positive T-LymphocytesCOVID-19 vaccineCancer VaccinesCell physiologyCellsCharacteristicsCold ChainsCommunicable DiseasesDataDisciplineDiseaseDisease remissionEarEndowmentEngineeringEpitheliumFailureFoundationsGoalsGossypiumHeadHumanHuman MicrobiomeImmuneImmune checkpoint inhibitorImmune responseImmune systemImmunityImmunologic AdjuvantsImmunologicsImmunologyImmunosuppressionInfectionIntravenousMalignant NeoplasmsMetastatic Neoplasm to the LungMethodsModalityModelingMucosal Immune ResponsesMucosal ImmunityMusNatureNeedlesOncologyOpportunistic InfectionsOrganismPatientsProcessPropertyRNA vaccineRegulatory T-LymphocyteRespiratory DiseaseSamplingSideSkinSolid NeoplasmSpecificityStaphylococcus epidermidisSurfaceSwabT-LymphocyteTNF geneTherapeuticTherapeutic UsesTissuesTopical applicationToxic effectTumor AntigensUpper respiratory tractVaccineeVaccinesVirus DiseasesVisionWild Type MouseWorkadaptive immune responseadaptive immunityanti-PD-1antigen-specific T cellsantiviral immunityautoimmune pathogenesiscancer cellcancer therapycell typechimeric antigen receptor T cellscommensal bacteriacostengineered T cellsimmune checkpoint blockadeimmune functionimmunoregulationinhibitorinnovationinsightlow and middle-income countriesmelanomamicrobiomeneoplastic cellnon-Nativenonhuman primatepandemic pathogenpatient subsetspreventprogramsresponsescaffoldside effectstandard of caresubcutaneoussuccesstooltumorvector vaccine
项目摘要
PROJECT SUMMARY/ABSTRACT
Eliciting or suppressing an adaptive immune response has become central to oncology, autoimmunity, and
infectious disease. Checkpoint inhibitors have revolutionized the treatment of cancer, while TNF inhibitors and
other immune-suppressive biologics have become the standard of care in autoimmune diseases. Vaccines are
a stunning accomplishment of biomedical research; the mRNA vaccines for SARS-2 are only the latest example.
CAR-T cells induce long-term remission in acute lymphoblastic leukemia, a previously incurable disease.
However, current methods for modulating adaptive immunity have serious limitations. Checkpoint inhibitors and
biologics only work in a subset of patients, and global stimulation or suppression of immune function frequently
leads to autoimmunity or opportunistic infection. Despite their extraordinary properties, many vaccines require a
needle and a cold chain, making them difficult to deploy in low- and middle-income countries, and they fail to
induce mucosal immunity, so vaccinated people can infect others. Engineered T cells have not been successful
against solid tumors to date, and ex vivo T cell engineering is costly and difficult to scale.
Here, we propose to address these challenges by tapping into the host’s ‘colonist interaction program’. Certain
bacterial strains from the microbiome elicit a strikingly potent, specific, and durable immune response. In a new
unpublished project in the lab that inspired the work we propose here, we showed that the anti-commensal
immune response can be redirected against the host by engineering commensal bacteria to express host
antigens on their surface. Commensal bacteria have all the key attributes of an ideal vaccine vector: they induce
highly potent, antigen-specific T and B cell responses; colonization is durable on the timescale of years to
decades (experimental evidence suggests the same is true for the immune response they elicit); and colonists
modulate immune function safely, in a way that spares host tissue from autoimmune attack.
Our vision is to create a general platform for eliciting a potent and durable adaptive immune response in a way
that is safe and inexpensive. The kernel of our idea is to develop a set of vaccine scaffolds in which a
commensal is the adjuvant and colonization is the mode of administration. We propose a four-part process
to build the foundations of commensal vaccines: Goal 1: identify a core set of commensals with immune
modulatory properties; Goal 2: optimize CD8+ T cell induction for antitumor therapy; Goal 3: enhance B cell
induction for preventing viral infection; and Goal 4: redirect colonist-specific Tregs against autoimmune disease.
These goals can proceed in parallel, and success in any one of them would have a great deal of impact. We
note that although this work is applied, it will create useful tools for basic research into immune modulation by
the microbiome, just as biologics and methods for T cell engineering have done for other sub-disciplines of
immunology.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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MICHAEL ANDREW FISCHBACH其他文献
MICHAEL ANDREW FISCHBACH的其他文献
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{{ truncateString('MICHAEL ANDREW FISCHBACH', 18)}}的其他基金
Virally-induced tumorigenesis controlled by the microbiota
由微生物群控制的病毒诱导的肿瘤发生
- 批准号:
10189532 - 财政年份:2019
- 资助金额:
$ 77.09万 - 项目类别:
Project 3: Microbiota generated aryl sulfates and secondary bile acids in cardiometabolic disease
项目 3:微生物群在心脏代谢疾病中产生芳基硫酸盐和次级胆汁酸
- 批准号:
10206257 - 财政年份:2019
- 资助金额:
$ 77.09万 - 项目类别:
Project 3: Microbiota generated aryl sulfates and secondary bile acids in cardiometabolic disease
项目 3:微生物群在心脏代谢疾病中产生芳基硫酸盐和次级胆汁酸
- 批准号:
10447071 - 财政年份:2019
- 资助金额:
$ 77.09万 - 项目类别:
Virally-induced tumorigenesis controlled by the microbiota
由微生物群控制的病毒诱导的肿瘤发生
- 批准号:
9751590 - 财政年份:2019
- 资助金额:
$ 77.09万 - 项目类别:
Virally-induced tumorigenesis controlled by the microbiota
由微生物群控制的病毒诱导的肿瘤发生
- 批准号:
10667586 - 财政年份:2019
- 资助金额:
$ 77.09万 - 项目类别:
Virally-induced tumorigenesis controlled by the microbiota
由微生物群控制的病毒诱导的肿瘤发生
- 批准号:
10425354 - 财政年份:2019
- 资助金额:
$ 77.09万 - 项目类别:
Project 3: Microbiota generated aryl sulfates and secondary bile acids in cardiometabolic disease
项目 3:微生物群在心脏代谢疾病中产生芳基硫酸盐和次级胆汁酸
- 批准号:
10653055 - 财政年份:2019
- 资助金额:
$ 77.09万 - 项目类别:
A complete map of the top 100 molecules from the gut microbiome
肠道微生物组前 100 个分子的完整图谱
- 批准号:
9162738 - 财政年份:2016
- 资助金额:
$ 77.09万 - 项目类别:
A complete map of the top 100 molecules from the gut microbiome
肠道微生物组前 100 个分子的完整图谱
- 批准号:
9540375 - 财政年份:2016
- 资助金额:
$ 77.09万 - 项目类别:
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