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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.

摘要