title: Nontyphoidal salmonella disease: Current status of vaccine research and development.
abstract: Among more than 2500 nontyphoidal Salmonella enterica (NTS) serovars, S. enterica serovar Typhimurium and S. enterica serovar Enteritidis account for approximately fifty percent of all human isolates of NTS reported globally. The global incidence of NTS gastroenteritis in 2010 was estimated to be 93 million cases, approximately 80 million of which were contracted via food-borne transmission. It is estimated that 155,000 deaths resulted from NTS in 2010. NTS also causes severe, extra-intestinal, invasive bacteremia, referred to as invasive nontyphoidal Salmonella (iNTS) disease. iNTS disease usually presents as a febrile illness, frequently without gastrointestinal symptoms, in both adults and children. Symptoms of iNTS are similar to malaria, often including fever (>90%) and splenomegaly (>40%). The underlying reasons for the high rates of iNTS disease in Africa are still being elucidated. Evidence from animal and human studies supports the feasibility of developing a safe and effective vaccine against iNTS. Both antibodies and complement can kill Salmonella species in vitro. Proof-of-principle studies in animal models have demonstrated efficacy for live attenuated and subunit vaccines that target the O-antigens, flagellin proteins, and other outer membrane proteins of serovars Typhimurium and Enteritidis. More recently, a novel delivery strategy for NTS vaccines has been developed: the Generalized Modules for Membrane Antigens (GMMA) technology which presents surface polysaccharides and outer membrane proteins in their native conformation. GMMA technology is self-adjuvanting, as it delivers multiple pathogen-associated molecular pattern molecules. GMMA may be particularly relevant for low- and middle-income countries as it has the potential for high immunologic potency at a low cost and involves a relatively simple production process without the need for complex conjugation. Several vaccines for the predominant NTS serovars Typhimurium and Enteritidis, are currently under development.
authors.affiliation: Center for Vaccine Development and Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Tennant
authors.affiliation: Jenner Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom; Wellcome Trust Sanger Institute, Wellcome Trust Genomes Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
authors.forename: Calman A
authors.initials: CA
authors.lastname: MacLennan
authors.affiliation: Center for Vaccine Development and Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Simon
authors.affiliation: GSK Vaccines Institute for Global Health, S.r.l. Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Martin
authors.affiliation: Center of Excellence in Woman and Child Health, The Aga Khan University, Stadium Road Karachi 74800, Pakistan. Electronic address: khan.m.imran@outlook.com.
authors.forename: M Imran
authors.initials: MI
authors.lastname: Khan
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000453:epidemiology / Q000517:prevention & control; D035843:Biomedical Research / Q000639:trends; D002986:Clinical Trials as Topic; D006801:Humans; D019081:O Antigens / Q000276:immunology; D000069452:Pathogen-Associated Molecular Pattern Molecules / Q000276:immunology; D012480:Salmonella Infections / Q000453:epidemiology / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000627:therapeutic use*; D012477:Salmonella enteritidis; D012486:Salmonella typhimurium; D022223:Vaccines, Subunit / Q000627:therapeutic use
chemical_list: D019081:O Antigens; D000069452:Pathogen-Associated Molecular Pattern Molecules; D022562:Salmonella Vaccines; D022223:Vaccines, Subunit
keywords: Africa; Developing countries; Pediatric infections; S. Enteritis; S. Typhimurium; Salmonella; Salmonella infections; Vaccine development; iNTS disease