Developing effective nanovaccines against pathogenic Escherichia coli

开发针对致病性大肠杆菌的有效纳米疫苗

基本信息

批准号：
10413247
负责人：
Alfredo G Torres
金额：
$ 19.75万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10413247
关键词：
Adherence Affect Antibodies Antibody titer measurement Antigens Attention Bacteria Binding Cells Child Coupled Couples Coupling Data Development Diarrhea Disease Disease Outbreaks Epithelial Cells Escherichia coli Escherichia coli EHEC Escherichia coli Infections Escherichia coli O157:H7 Fimbrial Adhesins Food Formulation Goals Hemolytic-Uremic Syndrome Hemorrhagic colitis Human Immune response Immunity Immunization Immunize Infection Infection prevention Injections Intestines Knowledge Lesion Link Mediating Mucosal Immune Responses Mus Outcome Pilum Play Preventive Process Property Proteins Reproducibility Research Role Serotyping Serum Shiga Toxin Subunit Vaccines Surface Testing Toxin Type III Secretion System Pathway Vaccinated Vaccines Variant Vegetables Virulence Virulence Factors Virulent Work base beef biothreat combat cross immunity diarrheal disease enteric infection enteric pathogen enteroaggregative Escherichia coli enteropathogenic Escherichia coli experimental study foodborne pathogen gut colonization immunogenic improved innovation insight intestinal epithelium microbiota mouse model mucosal vaccine nanoGold nanovaccine novel pathogen pathogenic Escherichia coli pathogenic bacteria prevent sound tissue tropism vaccine development

项目摘要

Abstract Our scientific contribution to the field of pathogenic Escherichia coli research has been to accelerate the development of an effective vaccine, using novel antigens and murine models of intestinal infection, that can not only protect against enterohemorrhagic E. coli (EHEC) O157:H7 but also prevent colonization of other pathogenic E. coli infections. Therefore, the long-term goal of our study is to provide new fundamental knowledge regarding pathogenic E. coli colonization, while elucidating protective immune responses that can be incorporated in the development of a vaccine. The central hypothesis of our proposal is that novel antigens coupled to nanovaccines will be immunogenic, and stimulation of protective antibodies will disrupt colonization by different pathogenic E. coli strains. This hypothesis is based on the strong experimental premise demonstrating that gold nanoparticles coupled to surface-exposed EHEC antigens (defined by our bio- immunoinformatic approach) elicited host immune responses that correlate with reduction in the intestinal colonization by EHEC O157:H7. Our progress in recent years demonstrated that coupling antigens to gold nanoparticles significantly enhances protective immunity against EHEC O157:H7 infection, and the serum from vaccinated mice reduces adherence/virulence of enteropathogenic E. coli O127:H6 and enteroaggregative E. coli O104:H4. Our proposed experimental approach will focus on two reproducible and scientifically sound aims: Optimize a gold nanoparticle vaccine containing antigens that prevent EHEC infections (Aim 1), and elucidate the immune responses required to prevent colonization and test cross-protective properties against other pathogenic E. coli strains (Aim 2). This work is significant because it is expected to provide advancement in the development of a fully protective gold nanoparticle vaccine that prevents infections caused by EHEC O157:H7, and such a vaccine will also be effective at targeting other pathogenic E. coli strains, without affecting the commensal E. coli microbiota. This study will elucidate the common links in the virulence mechanisms of these bacterial pathogens, which can then be used for the development of pathogenic E. coli- specific mucosal vaccines.

抽象的我们对致病性大肠杆菌研究领域的科学贡献是加速使用新型抗原和肠道感染的鼠模型开发有效的疫苗，可以不仅可以防止肠肠肠炎大肠杆菌（EHEC）O157：H7，还可以防止其他致病性大肠杆菌感染。因此，我们研究的长期目标是提供新的基本关于致病性大肠杆菌定植的知识，同时阐明可以保护性免疫反应纳入疫苗的开发中。我们建议的中心假设是新型抗原耦合到纳米雄将具有免疫原性，保护性抗体会破坏定殖通过不同的致病性大肠杆菌菌株。该假设基于强大的实验前提证明与表面暴露EHEC抗原结合的金纳米颗粒（由我们的生物定义免疫信息方法）引起与肠道减少相关的宿主免疫反应 EHEC O157：H7殖民化。近年来，我们的进展表明，将抗原耦合到黄金纳米颗粒可显着增强针对EHEC O157：H7感染的保护性免疫力，并从接种疫苗的小鼠降低了肠病大肠杆菌O127：H6和肠道肠道E.的依从性/毒力。大肠杆菌O104：H4。我们提出的实验方法将集中于两个可再现和科学的声音目的：优化含有预防EHEC感染的抗原的金纳米颗粒疫苗（AIM 1）和阐明防止定殖和测试跨保护特性所需的免疫反应其他致病性大肠杆菌菌株（AIM 2）。这项工作很重要，因为它有望提供进步在开发完全保护性金纳米粒子疫苗的过程中，该疫苗可防止EHEC引起的感染 O157：H7，这种疫苗也将有效靶向其他致病性大肠杆菌菌株，而无需影响共生大肠杆菌菌群。这项研究将阐明毒力中的共同联系这些细菌病原体的机制，然后可用于发育特定的粘膜疫苗。