Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: invasive nontyphoidal Salmonella disease (iNTS) [ICD11:
1A09 
, ICD11:
XN0QE ];
malaria [ICD11:
XN5FW ];
infection due to Salmonella enterica [ICD11:
XN5VC ]
Publication DOI: 10.1016/j.vaccine.2016.11.089Journal NLM ID: 8406899Publisher: Elsevier
Correspondence: francesca.x.micoli
gsk.com
Institutions: Dipartimento di Scienze della Vita, Ed. C11, Universita degli Studi di Trieste, via L. Giorgieri 1, 34127 Trieste, Italy, Antimicrobial Discovery Center, Department of Biology, Boston, MA, USA, Jenner Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK, GSK Vaccines Institute for Global Health (GVGH) S.r.l. (former Novartis Vaccines Institute for Global Health, NVGH), Via Fiorentina 1, 53100 Siena, Italy
Invasive nontyphoidal Salmonella disease (iNTS) is a leading cause of death and morbidity in Africa. The most common pathogens are Salmonella enterica serovars Typhimurium and Enteritidis. The O-antigen portion of their lipopolysaccharide is a target of protective immunity and vaccines targeting O-antigen are currently in development. Here we investigate the use of Generalized Modules for Membrane Antigens (GMMA) as delivery system for S. Typhimurium and S. Enteritidis O-antigen. Gram-negative bacteria naturally shed outer membrane in a blebbing process. By deletion of the tolR gene, the level of shedding was greatly enhanced. Further genetic modifications were introduced into the GMMA-producing strains in order to reduce reactogenicity, by detoxifying the lipid A moiety of lipopolysaccharide. We found that genetic mutations can impact on expression of O-antigen chains. All S. Enteritidis GMMA characterized had an O-antigen to protein w/w ratio higher than 0.6, while the ratio was 0.7 for S. Typhimurium ∆tolR GMMA, but decreased to less than 0.1 when further mutations for lipid A detoxification were introduced. Changes were also observed in O-antigen chain length and level and/or position of O-acetylation. When tested in mice, the GMMA induced high levels of anti-O-antigen-specific IgG functional antibodies, despite variation in density and O-antigen structural modifications. In conclusion, simplicity of manufacturing process and low costs of production, coupled with encouraging immunogenicity data, make GMMA an attractive strategy to further investigate for the development of a vaccine against iNTS.
O-antigen, Salmonella typhimurium, vaccine, Salmonella enteritidis, GMMA, Outer membrane vesicles
Structure type: polymer chemical repeating unit
Location inside paper: p.420, fig.1a
Compound class: O-antigen
Contained glycoepitopes: IEDB_127517,IEDB_130422,IEDB_130701,IEDB_135509,IEDB_135513,IEDB_135514,IEDB_135611,IEDB_136093,IEDB_136105,IEDB_136775,IEDB_136906,IEDB_137472,IEDB_137486,IEDB_141794,IEDB_142488,IEDB_144983,IEDB_144998,IEDB_146664,IEDB_151528,IEDB_152206,IEDB_153307,IEDB_190606,IEDB_225177,IEDB_840978,IEDB_885823,IEDB_983930,IEDB_983931,SB_192,SB_44,SB_67,SB_7,SB_72
Methods: SDS-PAGE, MALDI-MS, serological methods, HPAEC-PAD, immunization, immunogenicity in mice, HPLC-SEC/MALS
Related record ID(s): 12076
NCBI Taxonomy refs (TaxIDs): 90371
Show glycosyltransferases
There is only one chemically distinct structure:
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(later renamed to: Salmonella enterica ssp. enterica sv. Typhimurium O4,5)