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1. (CSDB ID: 11884) | report error |
| /Variants 0/-+ | /Variants 1/-+ | | | a-Abep2Ac-(1-3)-+ | | | | | -2)-a-D-Manp-(1-4)-a-L-Rhap-(1-3)-a-D-Galp-(1- /Variants 0/ is: a-D-Glcp-(1-6)- OR (exclusively) a-D-Glcp-(1-4)- /Variants 1/ is: Ac-3)- OR (exclusively) Ac-2)- | Show graphically |
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Salmonella enterica sv. Typhimurium O4,5
(later renamed to: Salmonella enterica ssp. enterica sv. Typhimurium O4,5)
(Ancestor NCBI TaxID 90371,
species name lookup)
, ICD11: XN0QE ]; malaria [ICD11: XN5FW ]; infection due to Salmonella enterica [ICD11: XN5VC ]
gsk.comInvasive 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|
2. (CSDB ID: 12076) | report error |
| a-Tyvp-(1-3)-+ a-D-Glcp-(1-4)-+ | | -2)-b-D-Manp-(1-4)-a-L-Rhap-(1-3)-a-D-Galp-(1- | Show graphically |
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Salmonella enterica sv. Enteritidis O9
(later renamed to: Salmonella enterica ssp. enterica sv. Enteritidis O9)
(Ancestor NCBI TaxID 149539,
species name lookup)
, ICD11: XN0QE ]; malaria [ICD11: XN5FW ]; infection due to Salmonella enterica [ICD11: XN5VC ]gsk.comInvasive 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|
3. (CSDB ID: 12891) | report error |
| 3HOBut3Me-(1-4)-b-D-Quip4N2Me-(1-3)-a-L-Rhap-(1-3)-a-L-Rhap-(1-2)-L-Rhap | Show graphically |
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Bacillus anthracis
(NCBI TaxID 1392,
species name lookup)
, ICD11: XN94F ]; infection due to Bacillus anthracis [ICD11: XN94F ]gsk.comThe tetrasaccharide (2-O-methyl-4-(3-hydroxy-3-methylbutamido)-4,6-dideoxy-α-D-glucopyranosyl-(1-3)-α-L-rhamnopyranosyl-(1-3)-α-L-rhamnopyranosyl-(1-2)-L-rhamnopyranose)from the major exosporium protein (BclA) of Bacillus anthracis has been proposed as a target for development of diagnostics and immune therapy or prophylaxis. While the immunodominant character of the anthrose residue has been previously elucidated, the role of the stereochemical configuration of the downstream rhamnose is unknown. Because the linkage of this residue to the GlcNAc bridging the glycan and the protein is lost during isolation of the tetrasaccharide, its alpha- and β-glycoforms have been synthesized. Herein, we prepared neoglycoconjugates from a series of fragments of the tetrasaccharide, including the complete alpha- and beta-tetrasaccharide glycoforms, a 2-demethoxylated version of the alpha-tetrasaccharide, and the alpha- and beta-trirhamnosides and CRM197. By immunization of mice, we showed that the anti alpha- and beta-tetrasaccharide serum equally recognized both glycoforms. In contrast the sera produced following immunization with the alpha- and beta-trirhamnoside fragments exhibited higher recognition for their own antigens than for their anomeric counterparts. The anti alpha- and beta-tetrasaccharide sera recognized Sterne spores in a comparable fashion. DBclA spores not expressing the major exosporium protein were also recognized by the same sera, while mutants that produced the carbohydrate antigen with deletion of either rhamnose or anthrose were not. The tetrasaccharide could, therefore, be expressed in proteins other than BlcA. This work proves that alpha- and beta-tetrasaccharide are equally potent immunogens.
carbohydrates, glycoconjugates, vaccines, Anthrose, Bacillus anthracis, B.anthracis, BclA, Diagnostics
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