title: A Highly Effective Component Vaccine against Nontyphoidal Salmonella enterica Infections.
abstract: Nontyphoidal Salmonella enterica (NTS) infections are a major burden to global public health, as they lead to diseases ranging from gastroenteritis to systemic infections and there is currently no vaccine available. Here, we describe a highly effective component vaccine against S. enterica serovar Typhimurium in both gastroenteritis and systemic murine infection models. We devised an approach to generate supernatants of S. enterica serovar Typhimurium, an organism that is highly abundant in virulence factors. Immunization of mice with this supernatant resulted in dramatic protection against a challenge with serovar Typhimurium, showing increased survival in the systemic model and decreased intestinal pathology in the gastrointestinal model. Protection correlated with specific IgA and IgG levels in the serum and specific secretory IgA levels in the feces of immunized mice. Initial characterization of the protective antigens in the bacterial culture supernatants revealed a subset of antigens that exhibited remarkable stability, a highly desirable characteristic of an effective vaccine to be used under suboptimal environmental conditions in developing countries. We were able to purify a subset of the peptides present in the supernatants and show their potential for immunization of mice against serovar Typhimurium resulting in a decreased level of colonization. This component vaccine shows promise with regard to protecting against NTS, and further work should significantly help to establish vaccines against these prevalent infections.
  
  
  OBJECTIVE
  Salmonella enterica infections other than typhoid and paratyphoid fever are a major global health burden, as they cause high morbidity and mortality worldwide. Strategies that prevent Salmonella-related diseases are greatly needed, and there is a significant push for the development of vaccines against nontyphoidal Salmonella enterica serovars. In this work, we describe an S. Typhimurium supernatant-derived vaccine that is effective in reducing bacterial colonization in mouse models of gastroenteritis as well as invasive disease. This is a component vaccine that shows high stability to heat, a feature that is important for use under suboptimal conditions, such as those found in sub-Saharan Africa.
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Rosana B R
authors.initials: RB
authors.lastname: Ferreira
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yanet
authors.initials: Y
authors.lastname: Valdez
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Coombes
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Subash
authors.initials: S
authors.lastname: Sad
authors.affiliation: Centre for High-Throughput Biology and Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Joost W
authors.initials: JW
authors.lastname: Gouw
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Brown
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Li
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada Institute of Medical Microbiology and Hospital Epidemiology Hannover Medical School, Hannover, Germany, and German Center for Infection Research.
authors.forename: Guntram A
authors.initials: GA
authors.lastname: Grassl
authors.affiliation: Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: L Caetano M
authors.initials: LC
authors.lastname: Antunes
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Navkiran
authors.initials: N
authors.lastname: Gill
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Mimi
authors.initials: M
authors.lastname: Truong
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Roland
authors.initials: R
authors.lastname: Scholz
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Reynolds
authors.affiliation: National Research Council Canada, Institute for Biological Sciences, Ottawa, Ontario, Canada.
authors.forename: Laskshmi
authors.initials: L
authors.lastname: Krishnan
authors.affiliation: National Research Council Canada, Institute for Biological Sciences, Ottawa, Ontario, Canada.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Zafer
authors.affiliation: Departament of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Sal-Man
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada Centre for Structural and Functional Genomics, Concordia University, Montreal, Québec, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lowden
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Sigrid D
authors.initials: SD
authors.lastname: Auweter
authors.affiliation: Centre for High-Throughput Biology and Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Foster
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada bfinlay@interchange.ubc.ca.
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D016470:Bacteremia / Q000382:microbiology / Q000517:prevention & control; D003470:Culture Media / Q000737:chemistry*; D004195:Disease Models, Animal; D005243:Feces / Q000737:chemistry; D005759:Gastroenteritis / Q000382:microbiology / Q000517:prevention & control; D007070:Immunoglobulin A / Q000097:blood; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007422:Intestines / Q000473:pathology; D051379:Mice; D012480:Salmonella Infections / Q000382:microbiology / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000008:administration & dosage* / Q000276:immunology* / Q000302:isolation & purification; D012486:Salmonella typhimurium / Q000254:growth & development / Q000276:immunology*; D016019:Survival Analysis; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification
chemical_list: D000907:Antibodies, Bacterial; D003470:Culture Media; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D022562:Salmonella Vaccines; D022223:Vaccines, Subunit