Initial clinical evaluation of attenuated Shigella flexneri 2a live vector expressing enterotoxigenic Escherichia coli antigens, strain CVD 1208S-122.

对表达产肠毒素大肠杆菌抗原(CVD 1208S-122 菌株)的福氏志贺氏菌 2a 活载体进行初步临床评估。

基本信息

  • 批准号:
    10212188
  • 负责人:
  • 金额:
    $ 152.92万
  • 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:
    2020-07-07 至 2024-04-30
  • 项目状态:
    已结题

项目摘要

Project Summary Shigella and enterotoxigenic Escherichia coli (ETEC) represent two important enteric pathogens. There are no vaccines to prevent both Shigella and ETEC. The Center for Vaccine Development's (CVD) mission to develop vaccines that prevent diarrheal disease in the most vulnerable populations has resulted in construction of a prototype Shigella-ETEC vaccine candidate strain, named CVD 1208S-122. Strain CVD 1208S-122 consists of an attenuated ΔguaBA, Δset, Δsen Shigella flexneri 2a strain that has been engineered to express ETEC colonization factor antigen I (CFA/I) and the B and A2 subunits of heat-labile enterotoxin (LThA2B) from genes integrated into the Shigella chromosome. The overall goal of this proposal is to conduct a proof-of-concept, randomized, double-blinded, placebo-controlled, dose-escalation Phase 1 clinical evaluation on a pilot cGMP lot of strain CVD 1208S-122. Each dose of the live, attenuated vaccine will be administered in the inpatient setting (Research Isolation Ward) and reactogenicity will be assessed over 96 hours (4 days) of direct observation. Stool cultures will be performed, vaccine strains will be isolated from stool, and blood and stool specimens will be analyzed for the immunologic responses to vaccination. This clinical trial is designed to be narrowly focused to provide the preliminary assessment of safety, answer whether the strain is stable, and evaluate the immunogenicity to our Shigella-ETEC combination vaccine approach. Aim1. Assess the safety and tolerability of CVD 1208S-122. Aim 2. Measure the excretion pattern, genetic stability, and transmissibility of CVD 1208S-122. Aim 3. Examine the immune response to CVD 1208S-122. These research aims will assessed within the context of a clinical trial to be conducted according to local legal and regulatory requirements, applicable US federal regulations, ICH guidelines, and Good Clinical Practice (GCP) standards. We have a plan for ensuring clinical monitoring, ongoing quality management with quality assurance and quality control activities, external independent safety oversight, and data management.
项目摘要 志贺氏菌和产肠毒素大肠杆菌(ETEC)是两种重要的肠道病原体。没有 预防志贺氏菌和ETEC的疫苗。疫苗开发中心(CVD)的使命是开发 在最脆弱的人群中预防疟疾的疫苗已经导致建立了一个 原型志贺氏菌-ETEC疫苗候选菌株,命名为CVD 1208 S-122。菌株CVD 1208 S-122由以下组成 一株经基因工程改造表达ETEC的减毒ΔguaBA、Δset、Δsen福氏志贺菌2a菌株 定植因子抗原I(CFA/I)和不耐热肠毒素(LThA 2 B)的B和A2亚单位 整合到志贺氏菌染色体中。本提案的总体目标是进行概念验证, 一项随机、双盲、安慰剂对照、剂量递增的试验性cGMP I期临床评价 菌株CVD 1208 S-122批次。每剂减毒活疫苗将在住院患者中接种。 将在96小时(4天)内对环境(研究隔离病房)和反应原性进行直接评估 观察.将进行粪便培养,从粪便、血液和粪便中分离疫苗株 将分析标本对疫苗接种的免疫应答。这项临床试验旨在 狭义地侧重于提供安全性的初步评估,回答菌株是否稳定,以及 评价志贺氏菌-ETEC联合疫苗方法的免疫原性。 目标1.评估CVD 1208 S-122的安全性和耐受性。 目标二。测量CVD 1208 S-122的排泄模式、遗传稳定性和可传递性。 目标3。检查对CVD 1208 S-122的免疫应答。 这些研究目的将根据当地法律的在临床试验的背景下进行评估 和法规要求、适用的美国联邦法规、ICH指南和药物临床试验质量管理规范 (GCP)标准我们有一个计划,以确保临床监测,持续的质量管理与质量 保证和质量控制活动、外部独立安全监督和数据管理。

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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Eileen M. Barry其他文献

Characterization of emShigella flexneri/em serotype 6 strains from geographically diverse low- and middle-income countries
来自不同地理区域的中低收入国家的 em 弗氏志贺菌 6 型菌株的特征描述
  • DOI:
    10.1128/mbio.02210-24
  • 发表时间:
    2024-11-29
  • 期刊:
  • 影响因子:
    4.700
  • 作者:
    Caitlin E. Gabor;Charlotte E. Chong;Jose M. Lemme-Dumit;Tracy H. Hazen;Kate S. Baker;Karen L. Kotloff;Irene N. Kasumba;Sharon M. Tennant;Henry Badji;M. Jahangir Hossain;Richard Omore;Benjamin Ochieng;Alex O. Awuor;Billy Ogwel;Jane Juma;Eileen M. Barry;David A. Rasko
  • 通讯作者:
    David A. Rasko
The 2022 Vaccines Against <em>Shigella</em> and Enterotoxigenic <em>Escherichia coli</em> (VASE) Conference: Summary of abstract-based presentations
  • DOI:
    10.1016/j.vaccine.2023.11.031
  • 发表时间:
    2024-03-07
  • 期刊:
  • 影响因子:
  • 作者:
    Soumalya Banerjee;Eileen M. Barry;Shahida Baqar;A. Louis Bourgeois;Joseph J. Campo;Robert K.M. Choy;Subhra Chakraborty;Allison Clifford;Carolyn Deal;Marcus Estrada;James Fleckenstein;Mateusz Hasso-Agopsowicz;William Hausdorff;Ibrahim Khalil;Nicole Maier;Cynthia Mubanga;James A. Platts-Mills;Chad Porter;Firadausi Qadri;Michelo Simuyandi
  • 通讯作者:
    Michelo Simuyandi
Clinical trials of Shigella vaccines: two steps forward and one step back on a long, hard road
志贺菌疫苗的临床试验:在漫长而艰难的道路上前进两步后退一步
  • DOI:
    10.1038/nrmicro1662
  • 发表时间:
    2007-07-01
  • 期刊:
  • 影响因子:
    103.300
  • 作者:
    Myron M. Levine;Karen L. Kotloff;Eileen M. Barry;Marcela F. Pasetti;Marcelo B. Sztein
  • 通讯作者:
    Marcelo B. Sztein
Genomic, transcriptomic, and phenotypic differences among archetype emShigella flexneri/em strains of serotypes 2a, 3a, and 6
血清型 2a、3a 和 6 的原型 em 福氏志贺氏菌菌株之间的基因组、转录组和表型差异
  • DOI:
    10.1128/msphere.00408-23
  • 发表时间:
    2023-11-28
  • 期刊:
  • 影响因子:
    3.100
  • 作者:
    Caitlin E. Gabor;Tracy H. Hazen;BreOnna C. Delaine-Elias;David A. Rasko;Eileen M. Barry;Vincent B. Young
  • 通讯作者:
    Vincent B. Young

Eileen M. Barry的其他文献

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{{ truncateString('Eileen M. Barry', 18)}}的其他基金

Advanced Development of a Combined Shigella-ETEC Vaccine
志贺氏菌-ETEC 联合疫苗的先进开发
  • 批准号:
    10704845
  • 财政年份:
    2023
  • 资助金额:
    $ 152.92万
  • 项目类别:
Initial clinical evaluation of attenuated Shigella flexneri 2a live vector expressing enterotoxigenic Escherichia coli antigens, strain CVD 1208S-122.
对表达产肠毒素大肠杆菌抗原(CVD 1208S-122 菌株)的福氏志贺氏菌 2a 活载体进行初步临床评估。
  • 批准号:
    10407441
  • 财政年份:
    2020
  • 资助金额:
    $ 152.92万
  • 项目类别:
An Expanded Multivalent Vaccine to Prevent MDR Shigella and ETEC Disease
预防 MDR 志贺氏菌和 ETEC 疾病的扩展多价疫苗
  • 批准号:
    10584477
  • 财政年份:
    2019
  • 资助金额:
    $ 152.92万
  • 项目类别:
An Expanded Multivalent Vaccine to Prevent MDR Shigella and ETEC Disease
预防 MDR 志贺氏菌和 ETEC 疾病的扩展多价疫苗
  • 批准号:
    10364710
  • 财政年份:
    2019
  • 资助金额:
    $ 152.92万
  • 项目类别:
Good Manufacturing Practices Master Cell and Working Cell Banks and GMP Pilot Lot of Prototype Shigella flexneri 2a live vector expressing enterotoxigenic E. coli antigens, CVD 1208S 122
良好生产规范主细胞和工作细胞库以及表达产肠毒素大肠杆菌抗原的福氏志贺氏菌 2a 活载体原型 GMP 中试批次,CVD 1208S 122
  • 批准号:
    9363198
  • 财政年份:
    2017
  • 资助金额:
    $ 152.92万
  • 项目类别:
Modeling Shigella Interaction with Innate Cells in Enteroid Co-Cultures to Inform Vaccine Development
模拟肠类共培养物中志贺氏菌与先天细胞的相互作用,为疫苗开发提供信息
  • 批准号:
    10427393
  • 财政年份:
    2016
  • 资助金额:
    $ 152.92万
  • 项目类别:
Modeling Shigella Interaction with Innate Cells in Enteroid Co-Cultures to Inform Vaccine Development
模拟肠类共培养物中志贺氏菌与先天细胞的相互作用,为疫苗开发提供信息
  • 批准号:
    10745566
  • 财政年份:
    2016
  • 资助金额:
    $ 152.92万
  • 项目类别:
Modeling Shigella Interaction with Innate Cells in Enteroid Co-Cultures to Inform Vaccine Development
模拟肠类共培养物中志贺氏菌与先天细胞的相互作用,为疫苗开发提供信息
  • 批准号:
    10190303
  • 财政年份:
    2016
  • 资助金额:
    $ 152.92万
  • 项目类别:
Correlates of Vaccine-Induced, Tunable-Protection in an Outbred Tularemia Model
远交兔热病模型中疫苗诱导的可调节保护的相关性
  • 批准号:
    9077642
  • 财政年份:
    2016
  • 资助金额:
    $ 152.92万
  • 项目类别:
Modeling Shigella Interaction with Innate Cells in Enteroid Co-Cultures to Inform Vaccine Development
模拟肠类共培养物中志贺氏菌与先天细胞的相互作用,为疫苗开发提供信息
  • 批准号:
    10686834
  • 财政年份:
    2016
  • 资助金额:
    $ 152.92万
  • 项目类别:

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治疗囊性纤维化患者 CFTR 调节剂治疗不良反应的个性化方法
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