title: Clinical Studies of Escherichia coli O157:H7 Conjugate Vaccines in Adults and Young Children.
abstract: Pediatric immunization has been the most effective measure to prevent and reduce the burden of infectious diseases in children. The recent inclusion of pneumococcal and meningococcal polysaccharide conjugates in infant immunization further reinforces their importance. Currently there is no human vaccine against enterohemorrhagic Escherichia coli (EHEC) infections. This review focuses on the human EHEC vaccine that has been studied clinically, in particular, the polysaccharide conjugate against E. coli O157. The surface polysaccharide antigen, O-specific polysaccharide, was linked to rEPA, recombinant exotoxin A of Pseudomonas aeruginosa. In adults and children 2 to 5 years old, O157-rEPA conjugates, shown to be safe, induced high levels of antilipopolysaccharide immunoglobulin G with bactericidal activities against E. coli O157, a functional bioassay that mimics the killing of inoculum in vivo. A similar construct using the B subunit of Shiga toxin (Stx) 1 as the carrier protein elicited both bactericidal and toxin-neutralizing antibodies in mice. So far there is no clinical study of Stx-based human vaccine. Passive immunization of Stx-specific antibodies with humanized, chimeric, or human monoclonal antibodies, produced in transgenic mice, showed promising data in animal models and offered high prospects. Demonstrations of their safety and effectiveness in treating hemolytic-uremic syndrome or patients with EHEC infections are under way, and results are much anticipated. For future development, other virulence factors such as the nontoxic Stx B subunit or intimin should be included, either as carrier protein in conjugates or as independent components. The additional antigens from O157 may provide broader coverage to non-O157 Stx-producing E. coli and facilitate both preventive and therapeutic treatment.
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Shousun Chen
authors.initials: SC
authors.lastname: Szu
authors.affiliation: Levine Children's Specialty Center-Pediatric Infectious Disease, Carolina Medical Centers, Charlotte, NC 28203.
authors.forename: Amina
authors.initials: A
authors.lastname: Ahmed
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics; D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001427:Bacterial Toxins / Q000235:genetics; D001770:Blood Bactericidal Activity; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D019453:Escherichia coli O157 / Q000235:genetics / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D005098:Exotoxins / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008822:Mice, Transgenic; D019081:O Antigens / Q000276:immunology; D016896:Treatment Outcome; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D022361:Escherichia coli Vaccines; D005098:Exotoxins; D007074:Immunoglobulin G; D019081:O Antigens; D018074:Vaccines, Conjugate; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A