title: An enterobacterial common antigen mutant of Salmonella enterica serovar Typhimurium as a vaccine candidate.
abstract: Due to increasing rates of invasive Salmonella enterica serovar Typhimurium infection, there is a need for an effective vaccine to prevent this disease. Previous studies showed that a mutation in the first gene of the Enterobacterial common antigen biosynthetic pathway, wecA, resulted in attenuation of S. Typhimurium in a murine model of salmonellosis. Furthermore, immunization with a wecA(-) strain protected against lethal challenge with the parental wild type S. Typhimurium strain. Herein, we examined whether the S. Typhimurium wecA(-) strain could also provide cross-protection against non-parental strains of S. Typhimurium and S. Enteritidis. We found that intraperitoneal immunization (IP) with S. Typhimurium SL1344 wecA(-) resulted in a significant increase in survival compared to control mice for all Salmonella challenge strains tested. Oral immunization with SL1344 wecA(-) also resulted in increased survival; however, protection was less significant than with intraperitoneal immunization. The increase in survival of SL1344 wecA(-) immunized mice was associated with a Salmonella-specific IgG antibody response. Furthermore, analysis of sera from IP and orally immunized animals revealed cross-reactive antibodies to numerous Salmonella isolates. Functional analysis of antibodies found within the sera from IP immunized animals revealed agglutination and opsonophagocytic activity against all tested O:4 Salmonella serovars. Together these results indicate that immunization with a S. Typhimurium wecA(-) strain confers protection against lethal challenge with wild type S. Typhimurium and S. Enteritidis and that immunization correlates with functional antibody production.
authors.affiliation: Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: dacie.bridge.ctr@usuhs.edu.
authors.forename: Dacie R
authors.initials: DR
authors.lastname: Bridge
authors.affiliation: Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: jeannette.whitmire@usuhs.edu.
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Whitmire
authors.affiliation: Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: Jeremy.Gilbreath@biofiredx.com.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Gilbreath
authors.affiliation: Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: eleanor.metcalf@usuhs.edu.
authors.forename: Eleanor S
authors.initials: ES
authors.lastname: Metcalf
authors.affiliation: Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: douglas.merrell@usuhs.edu.
authors.forename: D Scott
authors.initials: DS
authors.lastname: Merrell
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D056738:Cross Protection; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012480:Salmonella Infections / Q000276:immunology / Q000517:prevention & control; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology; D065288:Serogroup; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated; C017286:enterobacterial common antigen
keywords: Antibody; Live-attenuated; Salmonella Enteritidis; Salmonella Typhimurium; Vaccine; wecA