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Clinical Studies of O157:H7 Conjugate Vaccines in Adults and Young Children

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  • Authors: Shousun Chen Szu1, Amina Ahmed2
  • Editors: Vanessa Sperandio3, Carolyn J. Hovde4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 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
    • Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.EHEC-0016-2013
  • Received 26 August 2013 Accepted 27 August 2013 Published 07 November 2014
  • 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 (EHEC) infections. This review focuses on the human EHEC vaccine that has been studied clinically, in particular, the polysaccharide conjugate against 157. The surface polysaccharide antigen, O-specific polysaccharide, was linked to rEPA, recombinant exotoxin A of . 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 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 and facilitate both preventive and therapeutic treatment.

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

References

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35. Mohawk KL, Melton-Celsa AR, Robinson CM, O'Brien AD. 2010. Neutralizing antibodies to Shiga toxin type 2 (Stx2) reduce colonization of mice by Stx2-expressing Escherichia coli O157:H7. Vaccine 28:4777–4785. [PubMed][CrossRef]
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2014-11-07
2019-11-18

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 (EHEC) infections. This review focuses on the human EHEC vaccine that has been studied clinically, in particular, the polysaccharide conjugate against 157. The surface polysaccharide antigen, O-specific polysaccharide, was linked to rEPA, recombinant exotoxin A of . 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 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 and facilitate both preventive and therapeutic treatment.

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Figures

Clinical Studies of O157:H7 Conjugate Vaccines in Adults and Young Children
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Citation: Szu S, Ahmed A. 2014. Clinical studies of o157:h7 conjugate vaccines in adults and young children. microbiolspec 2(6): doi:10.1128/microbiolspec.EHEC-0016-2013
/content/microbiolspec/10.1128/microbiolspec.EHEC-0016-2013.fig1
FIGURE 1
Serum anti-Vi IgG response in healthy adults receiving one injection of OSP-rEPA (), DeALPS-rEPA (), or DeALPS-rEPA (); = 29 in each group.
microbiolspec/2/6/EHEC-0016-2013-fig1_thmb.gif
microbiolspec/2/6/EHEC-0016-2013-fig1.gif
Image of FIGURE 1

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FIGURE 1

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

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.EHEC-0016-2013
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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 (); = 25 in each group. No statistical difference between the groups at all periods.
microbiolspec/2/6/EHEC-0016-2013-fig2_thmb.gif
microbiolspec/2/6/EHEC-0016-2013-fig2.gif
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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 (); = 25 in each group. No statistical difference between the groups at all periods.

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.EHEC-0016-2013
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Download as Powerpoint

Tables

Clinical Studies of O157:H7 Conjugate Vaccines in Adults and Young Children
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Citation: Szu S, Ahmed A. 2014. Clinical studies of o157:h7 conjugate vaccines in adults and young children. microbiolspec 2(6): doi:10.1128/microbiolspec.EHEC-0016-2013
/content/microbiolspec/10.1128/microbiolspec.EHEC-0016-2013.T1
Table 1
Reciprocal bactericidal activity of serum LPS antibodies elicited in 2- to 5-year-old children injected with O157-rEPA conjugates
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Table 1

Reciprocal bactericidal activity of serum LPS antibodies elicited in 2- to 5-year-old children injected with O157-rEPA conjugates

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.EHEC-0016-2013
/content/microbiolspec/10.1128/microbiolspec.EHEC-0016-2013.T2
TABLE 2
Neutralization titers of Stx1 in sera from mice injected with O157 OSP conjugated with Stx1B
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TABLE 2

Neutralization titers of Stx1 in sera from mice injected with O157 OSP conjugated with Stx1B

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.EHEC-0016-2013

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