1 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.
2 Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada.
3 Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
4 Centre for High-Throughput Biology and Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, Canada.
5 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.
6 Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
7 National Research Council Canada, Institute for Biological Sciences, Ottawa, Ontario, Canada.
8 Departament of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
9 Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada Centre for Structural and Functional Genomics, Concordia University, Montreal, Québec, Canada.
10 Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada bfinlay@interchange.ubc.ca.

A Highly Effective Component Vaccine against Nontyphoidal Salmonella enterica Infections.

MBio. 2015 Sep 22;6(5):e01421-15

Authors: Ferreira RB, Valdez Y, Coombes BK, Sad S, Gouw JW, Brown EM, Li Y, Grassl GA, Antunes LC, Gill N, Truong M, Scholz R, Reynolds LA, Krishnan L, Zafer AA, Sal-Man N, Lowden MJ, Auweter SD, Foster LJ, Finlay BB

Abstract

UNLABELLED: 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.

IMPORTANCE: 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.

PMID: 26396246 [PubMed - indexed for MEDLINE]