A Yeast-based Immunotherapy against Clostridioides difficile infection
基于酵母的针对艰难梭菌感染的免疫疗法
基本信息
- 批准号:10380184
- 负责人:
- 金额:$ 93.27万
- 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
- 起止时间:2020-08-01 至 2023-10-31
- 项目状态:已结题
- 来源:
- 关键词:AnimalsAntibiotic ResistanceAntibioticsAttentionBiochemical GeneticsBiological ProductsBlood CirculationBusinessesCenters for Disease Control and Prevention (U.S.)Cessation of lifeChemicalsChimeric ProteinsClinicClinicalClinical Course of DiseaseClostridium difficileColonDNA cassetteDataDatabasesDevelopmentDevelopment PlansDiarrheaDoseDrug KineticsEncapsulatedEngineeringEnsureEnteralEpitopesExcipientsExotoxinsFamily suidaeFormulationFreezingFutureGenetic IdentityGnotobioticGoalsHumanImmunoglobulin AImmunoglobulin GImmunotherapyIn VitroIncidenceInfectionInflammationIntestinesLeadLifeModelingMusOralPharmaceutical PreparationsPhasePhenotypePhysiologyPowder dose formPreventionProbioticsProductionPropertyPseudomembranous ColitisPublic HealthRecurrenceRegulationSaccharomycesSafetySeverity of illnessSiteSmall Business Innovation Research GrantSystemTechnologyTestingTherapeuticTissuesToxicologyToxinTreatment EfficacyValidationVirulence FactorsYeastsanalytical methodantibiotic-associated diarrheaantitoxinbasecapsuleclinical developmentcolonization resistanceefficacy evaluationefficacy studyexperimental studygastrointestinalgenomic locushost colonizationimmunosuppressedmicrobiotanovelphase 2 studypillporcine modelpreclinical efficacypreventproduct developmentreconstitutionresistant strainresponsescreeningstandard care
项目摘要
Abstract
Antibiotic-resistant Clostridioides difficile is responsible for more than 29,000 deaths in the US each year and
the infection is an urgent threat (as designated by CDC) to public health. The incidence of C. difficile infection
(CDI) and disease severity is increasing in recent years due to the emergence of hypervirulent and antibiotic-
resistant strains. CDI is caused by the exotoxins TcdA and TcdB secreted by C. difficile in the colon of the
host. Current standard treatment with antibiotics is not optimal and is accompanied by a high recurrence rate
due to the disruption of host colonization resistance. Moreover, there is no approved prevention against the
infection. Our goal is to develop a novel yeast-based immunoprophylactic/therapeutic against both primary and
recurrent CDI. We have developed a therapeutic lead by engineering a probiotic yeast, Saccharomyces
boulardii (Sb), to secrete an antitoxin ABAB (Sb-ABAB). ABAB is a fusion protein of 4 VHHs targeting 2 distinct
neutralizing epitopes in TcdA and 2 in TcdB respectively. ABAB is ultrapotent in neutralizing both TcdA and
TcdB and broadly active against toxins from 64 clinical isolates. Our preliminary data showed that oral Sb-
ABAB protected mice from both primary and recurrent CDI. The objectives of this Fast-track SBIR are to: 1)
phenotypically and genetically characterize Sb-ABAB to ensure its identity and quality; 2) determine
pharmacokinetic and safety profiles of Sb-ABAB; 3) develop clinic-compatible formula of Sb-ABAB capsules;
and 4) perform IND-enabling efficacy study in a piglet model of CDI. All proposed activities will be guided by an
exceptional advisory/consultant team with specialized expertise in business development, biologics regulation,
product development and planning, and clinical development. Upon the completion of the proposed studies, we
will pursue Phase IIb for GMP manufacturing of Sb-ABAB, GLP toxicology and IND submission in the future.
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)
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Zhiyong Yang其他文献
Zhiyong Yang的其他文献
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{{ truncateString('Zhiyong Yang', 18)}}的其他基金
Novel Oral Yeast Immunotherapies for Ulcerative Colitis (Fast-track)
治疗溃疡性结肠炎的新型口服酵母免疫疗法(快速通道)
- 批准号:
10610406 - 财政年份:2022
- 资助金额:
$ 93.27万 - 项目类别:
Novel Oral Yeast Immunotherapies for Ulcerative Colitis (Fast-track)
治疗溃疡性结肠炎的新型口服酵母免疫疗法(快速通道)
- 批准号:
10399167 - 财政年份:2022
- 资助金额:
$ 93.27万 - 项目类别:
Novel Oral Yeast Immunotherapies for Ulcerative Colitis (Fast-track)
治疗溃疡性结肠炎的新型口服酵母免疫疗法(快速通道)
- 批准号:
10258297 - 财政年份:2021
- 资助金额:
$ 93.27万 - 项目类别:
A Yeast-based Immunotherapy against Clostridioides difficile infection
基于酵母的针对艰难梭菌感染的免疫疗法
- 批准号:
10337793 - 财政年份:2020
- 资助金额:
$ 93.27万 - 项目类别:
A Yeast-based Immunotherapy against Clostridioides difficile infection
基于酵母的针对艰难梭菌感染的免疫疗法
- 批准号:
10081622 - 财政年份:2020
- 资助金额:
$ 93.27万 - 项目类别:
A Yeast-based Immunotherapy against Clostridioides difficile infection
基于酵母的针对艰难梭菌感染的免疫疗法
- 批准号:
10523054 - 财政年份:2020
- 资助金额:
$ 93.27万 - 项目类别:
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