Extraintestinal Pathogenic Escherichia coli

Extaintestinal pathogenic Escherichia coli (ExPEC) cause a wide variety of infections in humans and domestic animals. This chapter will focus on ExPEC strains as they relate to humans. ExPEC are responsible for significant morbidity, mortality, and costs to our healthcare system. The development of an efficacious ExPEC vaccine will minimize disease and may be cost-effective in women with recurrent urinary tract infection (UTI) and probably other groups at risk for ExPEC infection such as the elderly. Surface polysaccharides, such as capsule, have been traditional targets for vaccine development. Because the surface polysaccharides present in various ExPEC strains exhibit significant antigenic heterogeneity, their use as vaccine candidates will be challenging. ExPEC adhesins (e.g., P fimbriae and the type 1 pilus), iron-regulated outer membrane proteins (e.g., IroN), and lipid A/core saccharides of lipopolysaccharide (LPS) have been identified as potential vaccine candidates and have been shown to confer protection in various animal infection models. Human phase 1 studies have been completed for the adhesin of the type 1 pilus (FimH and its chaperone protein FimC) and for detoxified J5 LPS (lipid A/core saccharides) complexed to Neisseria meningitidis group B outer membrane proteins, but no phase 2/3 data have been published. A variety of killed whole-cell vaccines, administered via the vaginal or oral route for the prevention of recurrent UTI, have been assessed in animal models and human clinical trials in Europe. These hold some promise, but require further evaluation. We envision that one option for a successful ExPEC vaccine will be the development of a polyvalent subunit vaccine comprising some combination of adhesins, outer membrane proteins, and perhaps detoxified lipid A/core saccharides of LPS. An alternative approach will be the development of a killed whole-cell vaccine that contains multiple strains of genetically engineered derivatives of pathogenic wild-type ExPEC designed to generate an optimal immune response. Development of either a polyvalent subunit vaccine or a genetically engineered killed whole-cell vaccine will be challenging. However, achieving this goal is important because of the medical–economic burden attributable to infections due to ExPEC.