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Research Article

Identification of a common immune signature in murine and human systemic Salmonellosis

Seung-Joo Lee, Li Liang, Silvia Juarez, Minelva R. Nanton, Esther N. Gondwe, Chisomo L. Msefula, Matthew A. Kayala, Francesca Necchi, Jennifer N. Heath, Peter Hart, Renée M. Tsolis, Robert S. Heyderman, Calman A. MacLennan, Philip L. Felgner, D. Huw Davies, and Stephen J. McSorley
  1. aCenter for Comparative Medicine, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, and
  2. gDepartment of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616;
  3. bDepartment of Medicine, University of California, Irvine, CA 92697;
  4. cMalawi-Liverpool-Wellcome Trust Clinical Research Program, College of Medicine, University of Malawi, PO Box 30096, Chichiri, Blantyre 3, Malawi;
  5. dInstitute for Genomics and Bioinformatics, University of California, Irvine, CA 92067;
  6. eNovartis Vaccines Institute for Global Health, 53100 Siena, Italy;
  7. fMedical Research Council Centre for Immune Regulation, School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom; and
  8. hLiverpool School of Tropical Medicine, University of Liverpool, Liverpool L3 5QA, United Kingdom

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PNAS first published February 13, 2012; https://doi.org/10.1073/pnas.1111413109
Seung-Joo Lee
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Li Liang
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Silvia Juarez
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Minelva R. Nanton
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Esther N. Gondwe
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Chisomo L. Msefula
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Matthew A. Kayala
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Francesca Necchi
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Jennifer N. Heath
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Peter Hart
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Renée M. Tsolis
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Robert S. Heyderman
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Calman A. MacLennan
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Philip L. Felgner
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D. Huw Davies
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Stephen J. McSorley
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  • For correspondence: sjmcsorley@ucdavis.edu
  1. Edited by Laurie H. Glimcher, Weill Cornell Medical College, New York, New York, and approved January 20, 2012 (received for review July 15, 2011)

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Abstract

Despite the importance of Salmonella infections in human and animal health, the target antigens of Salmonella-specific immunity remain poorly defined. We have previously shown evidence for antibody-mediating protection against invasive Salmonellosis in mice and African children. To generate an overview of antibody targeting in systemic Salmonellosis, a Salmonella proteomic array containing over 2,700 proteins was constructed and probed with immune sera from Salmonella-infected mice and humans. Analysis of multiple inbred mouse strains identified 117 antigens recognized by systemic antibody responses in murine Salmonellosis. Importantly, many of these antigens were independently identified as target antigens using sera from Malawian children with Salmonella bacteremia, validating the study of the murine model. Furthermore, vaccination with SseB, the most prominent antigenic target in Malawian children, provided mice with significant protection against Salmonella infection. Together, these data uncover an overlapping immune signature of disseminated Salmonellosis in mice and humans and provide a foundation for the generation of a protective subunit vaccine.

  • antigen discovery
  • non-Typhi Salmonella bacteremia

Footnotes

  • ↵1To whom correspondence should be addressed. E-mail: sjmcsorley{at}ucdavis.edu.
  • Author contributions: R.S.H., C.A.M., P.L.F., D.H.D., and S.J.M. designed research; S.-J.L., L.L., S.J., M.R.N., E.N.G., C.L.M., M.A.K., F.N., J.N.H., P.H., R.M.T., and D.H.D. performed research; L.L., R.S.H., P.L.F., and D.H.D. contributed new reagents/analytic tools; S.-J.L., L.L., R.M.T., C.A.M., P.L.F., D.H.D., and S.J.M. analyzed data; and C.A.M., D.H.D., and S.J.M. wrote the paper.

  • Conflict of interest statement: C.A.M. and F.N. are both employees of the Novartis Vaccines Institute for Global Health. C.A.M. has received grant support from GlaxoSmithKline.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1111413109/-/DCSupplemental.

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Identification of a common immune signature in murine and human systemic Salmonellosis
Seung-Joo Lee, Li Liang, Silvia Juarez, Minelva R. Nanton, Esther N. Gondwe, Chisomo L. Msefula, Matthew A. Kayala, Francesca Necchi, Jennifer N. Heath, Peter Hart, Renée M. Tsolis, Robert S. Heyderman, Calman A. MacLennan, Philip L. Felgner, D. Huw Davies, Stephen J. McSorley
Proceedings of the National Academy of Sciences Feb 2012, 201111413; DOI: 10.1073/pnas.1111413109

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Identification of a common immune signature in murine and human systemic Salmonellosis
Seung-Joo Lee, Li Liang, Silvia Juarez, Minelva R. Nanton, Esther N. Gondwe, Chisomo L. Msefula, Matthew A. Kayala, Francesca Necchi, Jennifer N. Heath, Peter Hart, Renée M. Tsolis, Robert S. Heyderman, Calman A. MacLennan, Philip L. Felgner, D. Huw Davies, Stephen J. McSorley
Proceedings of the National Academy of Sciences Feb 2012, 201111413; DOI: 10.1073/pnas.1111413109
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