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Enhancing C. difficile vaccination in the context of TcdB-mediated immunosuppression.

在 TcdB 介导的免疫抑制背景下加强艰难梭菌疫苗接种。

基本信息

批准号：
10625175
负责人：
Jimmy D. Ballard
金额：
$ 35.61万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-25 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10625175
关键词：
Adopted Amino Acid Sequence Animals Antibody Response Antigens Cells Cessation of life Clinical Trials Clostridium difficile Combined Vaccines Data Disease Drug Metabolic Detoxication Effectiveness Ensure Epitopes Event FDA approved Futility Generations Genetic Engineering Goals Hamsters Human Immune Immune response Immunologic Memory Immunosuppression Infection Investigation Mediating Memory Modeling Mus Phase III Clinical Trials Polysaccharides Production Proteins Publishing Relapse Reporting Rodent Structure Testing Toxic effect Toxin Toxoids Vaccinated Vaccination Vaccines Virulence Virulence Factors Work design experimental study gastrointestinal human monoclonal antibodies immune activation in vivo memory recall mouse model mutant neutralizing antibody next generation novel novel vaccines pathogen prevent response vaccine candidate vaccine effectiveness

项目摘要

PROJECT SUMMARY (Project 1) The most recent reports indicate Clostridioides difficile is the cause of over 400,000 cases of gastrointestinal illness and nearly 30,000 deaths annually. The goals of this project are to develop an effective next generation vaccine to prevent C. difficile disease and investigate the virulence-related activities of C. difficile that might reduce vaccine effectiveness. A leading candidate developed for vaccination in the Ballard lab is a mutant of TcdB lacking a key cell entry sequence. This mutant is unable to interact with cells but appears to retain aspects critical to promoting a neutralizing antibody response. This vaccine candidate will be further optimized and modified to ensure stability and a total absence of toxicity. Comparisons will be made between this mutant and a toxoid of TcdB. Next, the TcdB derivative will be used in combination with a polysaccharide antigen derived from C. difficile to generate a novel combination vaccine. All vaccine candidates will be tested for protection against C. difficile disease in a mouse model and the most promising of those will be further tested in a hamster model of infection. Using strains of C. difficile genetically engineered to express inactive TcdB, we will also determine if C. difficile inactivates key immune cells needed to provide effective memory responses in vaccinated animals. Together, these studies will both identify new C. difficile vaccines and determine the extent to which this pathogen can subvert their effectiveness.

项目总结（项目一）