Multivalent Adjuvant Immunization to Prevent Hospital Acquired Infections
Multivalent Adjuvant Immunization to Prevent Hospital Acquired Infections
批准号:
10378255
负责人:
BRAD J SPELLBERG
金额:
$99.51万
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
项目状态:
未结题
起止时间:
2020-02-10 至 2025-05-31
关键词:
Acinetobacter baumanniiAdjuvantAluminum HydroxideAntibiotic ResistanceAntimicrobial ResistanceBacteriaBiological AssayBiotechnologyBusinessesCandida albicansCause of DeathCenters for Disease Control and Prevention (U.S.)ClinicalClinical ProtocolsClinical TrialsContractsDangerousnessDataDiabetes MellitusDoseFDA approvedFundingFutureGlucansGoalsHealthHospitalsHumanImmuneImmunityImmunizationImmunotoxicologyIn VitroInfectionInfection preventionInflammasomeInnate Immune SystemKidney DiseasesKlebsiella pneumoniaeLeadLigationLipid AMannansMucormycosisMusNosocomial InfectionsParticulatePathway interactionsPatientsPeripheral Blood Mononuclear CellPharmaceutical PreparationsPhasePhase I Clinical TrialsPhase II/III TrialPhylogenetic AnalysisProtocols documentationRegimenRhizopusRiversScientistSmall Business Technology Transfer ResearchSourceSterilityTLR4 geneToxicologyUnited States Dept. of Health and Human ServicesVaccinationVaccine Clinical TrialVaccinesVendorbasecarbapenem resistanceclinical toxicologycostexperiencefungushealthcare-associated infectionsimmunotoxicitymacrophagemeetingsmembermethicillin resistant Staphylococcus aureusmouse modelnew technologynovel strategiesnovel vaccinesparticlepathogenpathogenic bacteriapathogenic fungusphase I trialpre-clinicalpreventprogramsscale upuptakevaccine developmentvaccine strategy
中文摘要
项目摘要/摘要
美国每年发生200万例医疗保健相关感染(HAI),导致9万名患者死亡和
成本约为500-1000亿美元(根据CPI调整为2020美元)。人类免疫缺陷是美国第六大死因,
领先于糖尿病和肾脏疾病。减少人类免疫缺陷病毒感染是美国卫生部和
人类服务1和专家呼吁采取包括接种疫苗在内的新战略来实现这一目标2
ExBaq是一家生物技术公司,由一个由科学家和商业同事组成的财团创立
多年来一直在研究抗药性医院病原体。ExBaq正在开发一种疫苗,以
预防血吸虫病由提供广谱保护的天然免疫刺激分子组成
抗跨王国HAI病原体感染(初步数据)。我们的疫苗包括:
A)氢氧化铝(Al(OH)3),它包含在FDA批准的多种疫苗中;以及
通过多种机制增强免疫力,包括诱导仓库形成,激活
NALP3炎症体,促进巨噬细胞对颗粒的摄取;
B)单磷脂A(MPL),它也包含(与Al(OH)3结合)
FDA批准的疫苗,并通过TLR4连接激活NF-κB途径;
C)甘露聚糖,它刺激各种先天和获得性免疫途径,在
非肠道给药时的临床试验。
在第一阶段,我们已经证实,这种三联佐剂方案具有最广泛的保护作用
病原体,提供较低的剂量(对商品成本很重要),与包含全菌的三联疗法相比
用葡聚糖颗粒代替甘露聚糖,或使用四重疗法(初步数据)。三位一体的功效
该方案已在耐碳青霉烯类抗生素的致死性鲍曼不动杆菌和
肺炎克雷伯菌、耐甲氧西林金黄色葡萄球菌(MRSA)和播散性感染
由真菌白色念珠菌和德拉玛根霉(毛霉病)引起。鉴于对革兰氏病的疗效-
对于阳性和阴性细菌和真菌病原体,我们的三价疫苗有可能预防
HAIS由最优先、耐药的院内病原菌引起。在建立了一个
最佳铅成分在第一阶段,第二阶段的目标是建立GMP,进行临床前免疫
毒理学研究,并完成支持IND提交的关键步骤。我们的目标是:
目标1:为我们的疫苗方案建立GMP生产。
目的2:完成临床前免疫毒性研究以支持IND应用。
目标3:在资金结束时完成支持IND备案的关键步骤。
英文摘要
PROJECT SUMMARY/ABSTRACT
Two million Healthcare Associated Infections (HAIs) occur per year in the US, killing >90,000 patients and
costing ~$50-100 billion (adjusted by CPI to 2020 dollars). HAIs are the 6th leading cause of death in the US,
ahead of diabetes and kidney disease. Reducing HAIs is a top priority of the US Department of Health and
Human Services1 and experts have called for novel strategies including vaccination to achieve this goal.2
ExBaq is a biotechnology company founded by a consortium of scientists and business colleagues who
have spent years studying antibiotic-resistant nosocomial pathogens. ExBaq is developing a vaccine to
prevent HAIs comprised of innate-immune stimulatory molecules that provide broad-spectrum protection
against infection caused by cross-kingdom HAI pathogens (preliminary data). Our vaccine consists of:
A) Aluminum hydroxide (Al(OH)3), which is contained in multiple FDA-approved vaccines, and
enhances immunity via multiple mechanisms, including induction of depot formation, activating the
NALP3 inflammasome, and enhancing particulate uptake by macrophages;
B) Monophosphoryl Lipid A (MPL), which is also contained (in combination with Al(OH)3) in multiple
FDA-approved vaccines and activates the NF-κB pathway via TLR4 ligation;
C) Mannan, which stimulates a variety of innate and adaptive immune pathways, and was safe in
clinical trials when administered parenterally.
During Phase I we have confirmed that this triple adjuvant regimen has the broadest protection against
pathogens, affording lower doses (important for cost of goods), compared to a triple regimen containing whole
glucan particles instead of mannan, or with a quadruple regimen (preliminary data). Efficacy of the triple
regimen has been confirmed in lethal mouse models of carbapenem-resistant Acinetobacter baumannii and
Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and disseminated infection
caused by the fungi Candida albicans and Rhizopus delamar (mucormycosis). Given efficacy against Gram-
positive and -negative bacteria and fungal pathogens, our trivalent vaccine has potential to prevent
HAIs caused by the highest priority, antibiotic-resistant nosocomial pathogens. Having established an
optimal lead composition in Phase I, the goal of Phase II is to establish GMP, conduct pre-clinical immuno-
toxicology studies, and to complete key steps to supporting IND submission. Our Aims are to:
AIM 1: Establish GMP manufacturing for our vaccine regimen.
AIM 2: To complete pre-clinical immuno-toxicity studies to support an IND application.
AIM 3: Complete key steps to support IND-filing at end of funding.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Multivalent Adjuvant Immunization to Prevent Hospital Acquired Infections
-
批准号:9899885
-
项目类别:
-
资助金额:$30.0万
-
财政年份:2020
-
负责人:BRAD J SPELLBERG
-
依托单位:
Multivalent Adjuvant Immunization to Prevent Hospital Acquired Infections
-
批准号:10646147
-
项目类别:
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资助金额:$98.94万
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财政年份:2020
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负责人:BRAD J SPELLBERG
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依托单位:
Diabetes and Inflammation During Infection
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批准号:9223117
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项目类别:
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资助金额:$20.63万
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负责人:BRAD J SPELLBERG
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依托单位:
The Surface of Hospitals Intensive Environmental Load Disinfection (SHIELD) Study
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批准号:10013217
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项目类别:
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财政年份:2017
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负责人:BRAD J SPELLBERG
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依托单位:
MAb Passive Vaccination against Acinetobacter baumannii
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批准号:10518413
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项目类别:
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资助金额:$75.09万
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财政年份:2017
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负责人:BRAD J SPELLBERG
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依托单位:
MAb Passive Vaccination against Acinetobacter baumannii
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批准号:9440295
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财政年份:2017
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负责人:BRAD J SPELLBERG
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MAb Passive Vaccination against Acinetobacter baumannii
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财政年份:2017
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依托单位:
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批准号:9003590
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依托单位:
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