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PMID: 22331879 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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 ·Vol. 109 ·No. 13 ·2012-03-27 ·Pages 4998-5003

Lee SJ, Liang L, Juarez S, Nanton MR, Gondwe EN, Msefula CL, Kayala MA, Necchi F, Heath JN, Hart P, Tsolis RM, Heyderman RS, MacLennan CA, Felgner PL, Davies DH, McSorley SJ

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.

MeSH Terms
Animals Antibody Formation/immunology Antigens, Bacterial/immunology Bacterial Proteins/immunology Blood Bactericidal Activity Child Child, Preschool Convalescence Female Humans Infant Infant, Newborn Malawi Male Mice Mice, Inbred Strains Protein Array Analysis Reproducibility of Results Salmonella Infections/blood,immunology Salmonella Infections, Animal/immunology Vaccination Vaccines, Attenuated/immunology Vaccines, Subunit/immunology
Chemicals
Antigens, Bacterial Bacterial Proteins Vaccines, Attenuated Vaccines, Subunit
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Lee Seung-Joo
Center for Comparative Medicine, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Liang Li
Juarez Silvia
Nanton Minelva R
Gondwe Esther N
Msefula Chisomo L
Kayala Matthew A
Necchi Francesca
Heath Jennifer N
Hart Peter
Tsolis Renée M
Heyderman Robert S
MacLennan Calman A
Felgner Philip L
Davies D Huw
McSorley Stephen J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
Published
2012-03-27
Epub
2012-00-13
Pages
4998-5003
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC3324033
Subset
IM
Grants
NIAID NIH HHS · AI55743 · United States
NIAID NIH HHS · R01 AI073672 · United States
NIAID NIH HHS · R01 AI055743 · United States
Medical Research Council · G9818340 · United Kingdom
NIAID NIH HHS · U54 AI065359 · United States
Wellcome Trust · 067902/Z/02/Z · United Kingdom
NIAID NIH HHS · F31 AI091298 · United States
NLM NIH HHS · T15 LM007443 · United States
NLM NIH HHS · LM-07443-01 · United States
NIAID NIH HHS · AI073672 · United States
NIAID NIH HHS · AI091298 · United States
Wellcome Trust · 084679/Z/08/Z · United Kingdom
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