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Vaccines

Serum Bactericidal Assays To Evaluate Typhoidal and Nontyphoidal Salmonella Vaccines

Mary Adetinuke Boyd, Sharon M. Tennant, Venant A. Saague, Raphael Simon, Khitam Muhsen, Girish Ramachandran, Alan S. Cross, James E. Galen, Marcela F. Pasetti, Myron M. Levine
D. L. Burns, Editor
Mary Adetinuke Boyd
aCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA
cDepartment of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Sharon M. Tennant
aCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA
bDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Venant A. Saague
aCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA
bDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Raphael Simon
aCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA
bDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Khitam Muhsen
aCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA
bDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Girish Ramachandran
aCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA
bDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Alan S. Cross
aCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA
bDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
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James E. Galen
aCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA
bDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Marcela F. Pasetti
aCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA
cDepartment of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Myron M. Levine
aCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA
bDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
cDepartment of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA
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D. L. Burns
Roles: Editor
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DOI: 10.1128/CVI.00115-14
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ABSTRACT

Invasive Salmonella infections for which improved or new vaccines are being developed include enteric fever caused by Salmonella enterica serovars Typhi, Paratyphi A, and Paratyphi B and sepsis and meningitis in young children in sub-Saharan Africa caused by nontyphoidal Salmonella (NTS) serovars, particularly S. enterica serovars Typhimurium and Enteritidis. Assays are needed to measure functional antibodies elicited by the new vaccines to assess their immunogenicities and potential protective capacities. We developed in vitro assays to quantify serum bactericidal antibody (SBA) activity induced by S. Typhi, S. Paratyphi A, S. Typhimurium, and S. Enteritidis vaccines in preclinical studies. Complement from various sources was tested in assays designed to measure antibody-dependent complement-mediated killing. Serum from rabbits 3 to 4 weeks of age provided the best complement source compared to serum from pigs, goats, horses, bovine calves, or rabbits 8 to 12 weeks of age. For S. Enteritidis, S. Typhimurium, and S. Typhi SBA assays to be effective, bacteria had to be harvested at log phase. In contrast, S. Paratyphi A was equally susceptible to killing whether it was grown to the stationary or log phase. The typhoidal serovars were more susceptible to complement-mediated killing than were the nontyphoidal serovars. Lastly, the SBA endpoint titers correlated with serum IgG anti-lipopolysaccharide (LPS) titers in mice immunized with mucosally administered S. Typhimurium, S. Enteritidis, and S. Paratyphi A but not S. Typhi live attenuated vaccines. The SBA assay described here is a useful tool for measuring functional antibodies elicited by Salmonella vaccine candidates.

FOOTNOTES

    • Received 4 March 2014.
    • Accepted 10 March 2014.
    • Accepted manuscript posted online 12 March 2014.
  • Supplemental material for this article may be found at http://dx.doi.org/10.1128/CVI.00115-14.

  • Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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Serum Bactericidal Assays To Evaluate Typhoidal and Nontyphoidal Salmonella Vaccines
Mary Adetinuke Boyd, Sharon M. Tennant, Venant A. Saague, Raphael Simon, Khitam Muhsen, Girish Ramachandran, Alan S. Cross, James E. Galen, Marcela F. Pasetti, Myron M. Levine
Clinical and Vaccine Immunology May 2014, 21 (5) 712-721; DOI: 10.1128/CVI.00115-14

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Serum Bactericidal Assays To Evaluate Typhoidal and Nontyphoidal Salmonella Vaccines
Mary Adetinuke Boyd, Sharon M. Tennant, Venant A. Saague, Raphael Simon, Khitam Muhsen, Girish Ramachandran, Alan S. Cross, James E. Galen, Marcela F. Pasetti, Myron M. Levine
Clinical and Vaccine Immunology May 2014, 21 (5) 712-721; DOI: 10.1128/CVI.00115-14
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