Immunology and Immunochemistry of Synthetic and Semisynthetic <i>Salmonella</i> O-Antigen-Specific Glycoconjugates

Lindberg, Alf A.; Wollin, Ralfh; Bruse, Gert W.; Ekwall, Erik; Svenson, Stefan B.

doi:10.1021/bk-1983-0231.ch005

Cited by 28 publications

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“…This is consistent with the common notion that the oligosaccharide component of a conjugate vaccine is often required to have a length in excess of ten residues [5][6][7]. Kabat found that the antidextran antibodies combining site is able to accommodate oligosaccharide composed of up to seven sugar residues [8], Lindberg in his pioneering work showed that octa-and dodecasaccharides isolated by phage mediated degradation of Salmonella O-polysaccharide were optimal for evoking a protective response [9]. Recent studies with synthetic oligosaccharide vaccines have confirmed that 3 repeating units composed of 12-15 monosaccharide residues are preferred over smaller structures for production of protective antibody [7,10].…”

Section: Introductionsupporting

confidence: 80%

A structurally diversified linker enhances the immune response to a small carbohydrate hapten

et al. 2011

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The tether employed to covalently attach β-mannan disaccharide glycoconjugates influences the specificity of rabbit antibodies that protect against Candida albicans. Two glycoconjugates containing (1 → 2)-β-mannan disaccharides linked to chicken serum albumin (CSA) either via a structurally uniform or via a stereodiversified spacer were prepared and evaluated in immunization trials in mice and rabbits. Immunization with conjugate vaccine possessing a structurally diversified linker induced higher IgG titers against Candida albicans cell wall phosphomannan than a conjugate with a structurally uniform linker. These results suggest that affinity maturation and the specific antibody response can be shifted towards recognition of the desired hapten by employing a linker with diversified configuration.

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Section: Introductionsupporting

confidence: 80%

A structurally diversified linker enhances the immune response to a small carbohydrate hapten

et al. 2011

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“…Increased body temperature after LPS injection has been reported in rabbits (Lindberg et al, 1983), chickens (Klasing et al, 1987a), humans (Michie et al, 1988), and sheep (Sloane et al, 1992). The febrile response has been related to an increased production of the cytokines interleukin-1 (Klasing et al, 1987a) and tumor necrosis factor (Kettelhut et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Effects of Early Immune Stress and Changes in Dietary Metabolizable Energy on the Development of Newly Hatched Turkeys.

et al. 1995

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Two experiments were conducted to document the effects of an early immunologic stress and changes in dietary ME(n) on growth and nutrient utilization of newly hatched turkeys. Treatments in both experiments consisted of a complete factorial arrangement of two types of injection and four isonitrogenous diets. Turkeys were injected i.p. with saline (SAL) or a solution of lipopolysaccharide (LPS) (100 micrograms LPS/mL SAL) at 1, 3, and 5 d of age. In Experiment 1, two diets were formulated to contain 2,800 kcal ME(n)/kg. One was a corn-soybean meal-based diet (CSBM) and the other contained 8% Solkafloc (SKF). A third diet (3,100 kcal ME(n)/kg) was formulated by substituting 8% sucrose (SUC) for the 8% SKF. The fourth diet included in Experiment 1 was formulated to contain 3,700 kcal ME(n)/kg. The CSBM and SUC diets were also included in Experiment 2. Two additional diets tested in Experiment 2 were the CSBM diet containing 74.5 mg ibuprofen/kg (IBU) and a corn-soybean meal-based diet with a ME(n) value of 3,100 kcal/kg (CS31). Injection with LPS reduced (P < .05) BW of turkeys throughout Experiment 1 and until 9 d of age in Experiment 2, as compared with injection with SAL, irrespective of dietary treatment. The reduction in BW was mainly due to a decrease in feed intake (FI) (P < .05). Turkeys fed diets with 3,100 kcal ME(n)/kg were heavier (P < .05) than those fed diets with 2,800 kcal ME(n)/kg, irrespective of injection. Inclusion of ibuprofen to the CSBM diet from 1 to 14 d improved (P < .05) BW and feed efficiency (P < .01) of turkeys at 14 d of age, compared with turkeys fed the CSBM diet. Determined ME(n) was not affected by LPS injection. Adverse effects of LPS injection on growth of turkey poults were mainly the consequence of a reduced FI and not of altered nutrient utilization. These effects were not fully alleviated by feeding a diet with 3,100 kcal ME(n)/kg.

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“…Such saccharides may be required for the production of synthetic vaccines. S. entericu 0-antigen-specific oligosaccharides have also been produced by enzymatic degradation of the polysaccharide, utilizing bacteriophage glycosidases [4]. So far this procedure has yielded oligosaccharides (monotetramers, ditetramers, tritetramers, and tetramers of a tetrasaccharide) which have terminal sugars different from those of the natural biological repeating unit.…”

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Enzymatic synthesis and isolation of thymidine diphosphate‐6‐deoxy‐D‐xylo‐4‐hexulose and thymidine diphosphate‐L‐rhamnose

Marumo

Lindqvist

Verma

et al. 1992

European Journal of Biochemistry

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A two-step enzymatic synthesis of dTDP-L-rhamnose is developed using enzymes from sonicated extracts of cultures of Escherichia coli K12 strains harboring plasmids containing different parts of the rjb gene cluster of Salmonella enterica LT2. The intermediate dTDP-6-deoxy-~-xylo-4-hexulose was isolated after a 1 -h reaction, using only dTDP-D-glucose and dTDP-D-glucose 4,6-dehydratase, followed by protein precipitation and desalting by gel chromatography (yield 89Y0). In a two-step reaction using dTDP-D-glucose and dTDP-D-glucose 4,6-dehydratase in the first step, and with NADPH, dTDP-6-deoxy-~-xylo-4-hexulose 3,5-epimerase and NADPH : dTDP-6-deoxy-~-l.vxo-4-hexulose-4-reductase in the second hour of incubation, the dTDP-D-glucose was fully converted to dTDP-L-rhamnose. The hexoses of both products were identified by mass spectroscopy. The molar yield of dTDP-L-rhamnose, after protein precipitation, anion-exchange chromatography and desalting by gel chromatography, was ~W O , corresponding to more than 150 mg, starting from 250 mg of dTDP-D-glucose. When stored lyophilysed under nitrogen, these products were found to be stable for several months. Both dTDP-6-deoxy-~-xylo-4-hexulose and dTDP-L-rhamnose have light absorption maxima at 267 nm, with molar absorption coefficients close to that of dTMP. However, the absorption coefficient of dTDP-6-deoxy-~-.xylo-4-hexulose at the absorption maximum of 320 nm (specific for sugars containing keto groups) was found to be approximately 20% higher than values presented earlier.Furthermore, an HPLC technique is presented for determining the net activity of dTDP-6-deoxy-~-xy/o-4-hexulose 3,5-epimerase and NADPH : dTDP-6-deoxy-~-lyxo-4-hexulose-4-reductase, based on separation of dTDP-6-deoxy-~-xylo-4-hexulose and dTDP-L-rhamnose. The HPLC technique is also suitable for determination of all the nucleotide components involved in the synthesis.The 0 antigen part of the lipopolysaccharide of Salmonella enterica sero-group B strains has a saccharide chain built of site interaction. Therefore, isolated saccharides are important for elucidation of host-defence mechanisms.In recent years advances have been made in the chemical synthesis of saccharides [3]. However, saccharide synthesis is still a relatively complicated procedure, in particular when saccharides larger than the tetrasaccharides shown above are to be synthesized and synthesis is required in large quantities. Such saccharides may be required for the production of synthetic vaccines. S. entericu 0-antigen-specific oligosaccharides have also been produced by enzymatic degradation of the polysaccharide, utilizing bacteriophage glycosidases [4]. So far this procedure has yielded oligosaccharides (monotetramers, ditetramers, tritetramers, and tetramers of a tetrasaccharide) which have terminal sugars different from those of the natural biological repeating unit. We have therefore investigating the feasability of enzymatic synthesis of the S. enterica 0-antigenspecific oligosaccharide using enzymes overproduced by cloned gene...

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Immunology and Immunochemistry of Synthetic and Semisynthetic Salmonella O-Antigen-Specific Glycoconjugates

Cited by 28 publications

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A structurally diversified linker enhances the immune response to a small carbohydrate hapten

A structurally diversified linker enhances the immune response to a small carbohydrate hapten

Effects of Early Immune Stress and Changes in Dietary Metabolizable Energy on the Development of Newly Hatched Turkeys.

Enzymatic synthesis and isolation of thymidine diphosphate‐6‐deoxy‐D‐xylo‐4‐hexulose and thymidine diphosphate‐L‐rhamnose

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