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, Renee M Tsolis, Robert S. Heyderman, Calman A. MacLennan, Philip L. Felgner, D. Huw Davies, Stephen J Mcsorley

Research output: Contribution to journalArticle

62 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4998-5003
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number13
DOIs
StatePublished - Mar 27 2012

Keywords

  • Antigen discovery
  • Non-Typhi Salmonella bacteremia

ASJC Scopus subject areas

  • General

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    Lee, S. J., Liang, L., Juarez, S., Nanton, M. R., Gondwe, E. N., Msefula, C. L., Kayala, M. A., Necchi, F., Heath, J. N., Hart, P., Tsolis, R. M., Heyderman, R. S., MacLennan, C. A., Felgner, P. L., Davies, D. H., & Mcsorley, S. J. (2012). Identification of a common immune signature in murine and human systemic Salmonellosis. Proceedings of the National Academy of Sciences of the United States of America, 109(13), 4998-5003. https://doi.org/10.1073/pnas.1111413109