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
项目概要/摘要
在美国,每年发生200万起医疗相关感染(HAI),导致> 90,000名患者死亡,
成本约为500 - 1000亿美元(按CPI调整至2020年美元)。HAI是美国第六大死亡原因,
糖尿病和肾病的发病率。减少HAI是美国卫生部的首要任务,
人类服务1和专家呼吁采取包括疫苗接种在内的新策略来实现这一目标。
ExBaq是一家生物技术公司,由一群科学家和商业同事创立,
花了数年时间研究耐药性医院病原体。ExBaq正在开发一种疫苗,
预防由提供广谱保护的先天免疫刺激分子组成的HAI
对抗由跨王国HAI病原体引起的感染(初步数据)。我们的疫苗包括:
A)氢氧化铝(Al(OH)3),其包含在多种FDA批准的疫苗中,以及
通过多种机制增强免疫力,包括诱导储库形成,激活
NALP 3炎性体,并增强巨噬细胞的颗粒摄取;
B)单磷酰脂质A(MPL),其也被包含在多个(与Al(OH)3组合的)组合物中。
FDA批准的疫苗,并通过TLR 4连接激活NF-κB通路;
C)甘露聚糖,它刺激各种先天性和适应性免疫途径,并且在
临床试验时,给药胃肠外。
在第一阶段,我们已经证实,这种三重辅助治疗方案具有最广泛的保护,
病原体,提供较低的剂量(重要的商品成本),相比,三重方案含有整个
葡聚糖颗粒代替甘露聚糖,或使用四重方案(初步数据)。三重功效
方案已在碳青霉烯类耐药鲍曼不动杆菌致死小鼠模型中得到证实,
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
由白色念珠菌和绿根霉引起的毛霉病。鉴于对革兰氏阴性菌的有效性-
阳性和阴性的细菌和真菌病原体,我们的三价疫苗有可能预防
HAI由最高优先级的耐药医院病原体引起。建立了一个
第一阶段是最佳的铅成分,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:
目的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申请。
目标3:完成关键步骤,以支持在资助结束时提交IND。
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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负责人:BRAD J SPELLBERG
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MAb Passive Vaccination against Acinetobacter baumannii
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批准号:9756135
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财政年份:2017
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依托单位:
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