Developing effective nanovaccines against pathogenic Escherichia coli

点击翻译按钮获取中文摘要

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.