Clinical Studies of Escherichia coli O157:H7 Conjugate Vaccines in Adults and Young Children
- Authors: Shousun Chen Szu1, Amina Ahmed2
- Editors: Vanessa Sperandio3, Carolyn J. Hovde4
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VIEW AFFILIATIONS HIDE AFFILIATIONSAffiliations: 1: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; 2: Levine Children's Specialty Center—Pediatric Infectious Disease, Carolina Medical Centers, Charlotte, NC 28203; 3: University of Texas Southwestern Medical Center, Dallas, TX; 4: University of Idaho, Moscow, ID
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Received 26 August 2013 Accepted 27 August 2013 Published 07 November 2014
- Correspondence: Shousun C. Szu, [email protected]

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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.
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Citation: Szu S, Ahmed A. 2014. Clinical Studies of Escherichia coli O157:H7 Conjugate Vaccines in Adults and Young Children. Microbiol Spectrum 2(6):EHEC-0016-2013. doi:10.1128/microbiolspec.EHEC-0016-2013.




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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.

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Figures




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FIGURE 1
Serum anti-Vi IgG response in healthy adults receiving one injection of OSP-rEPA (), DeALPS-rEPA1 (
), or DeALPS-rEPA2 (
); n = 29 in each group.



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FIGURE 2
Serum anti-Vi IgG response in children 2 to 5 years old receiving one injection () or a booster dose 6 weeks later (
); n = 25 in each group. No statistical difference between the groups at all periods.
Tables

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Table 1
Reciprocal bactericidal activity of serum LPS antibodies elicited in 2- to 5-year-old children injected with E. coli O157-rEPA conjugates a

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TABLE 2
Neutralization titers of Stx1 in sera from mice injected with E. coli O157 OSP conjugated with Stx1B
Supplemental Material
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