The synthesis of Streptococcus pneumoniae polysaccharide-tetanus toxoid conjugates and the effect of chain length on immunogenicity

Laferrière, Craig A.; Sood, Ramesh K.; Muys, Jean-Marc de; Michon, Francis; Jenning, Harold J.

doi:10.1016/s0264-410x(96)00148-x

Cited by 63 publications

(45 citation statements)

References 33 publications

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“…The hexadecamer was the most immunogenic; the small increment in immunogenicity of the hexadecamer over the dodecamer at comparable densities suggests that there will be (38,39). The immunogenicity of our synthetic saccharide conjugates likely involves the interaction of both B-cells and T-cells (40).…”

Section: Resultsmentioning

confidence: 86%

Protein conjugates of synthetic saccharides elicit higher levels of serum IgG lipopolysaccharide antibodies in mice than do those of the O-specific polysaccharide fromShigella dysenteriaetype 1

Pozsgay

Chu

Pannell

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

169

128

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Our development of vaccines to prevent shigellosis is based on the hypothesis that a critical ( The average molar ratios of the saccharides to HSA ranged from 4 to 24. Serum IgG anti-LPS, elicited in mice by O-SP-HSA or synthetic tetra-, octa-, dodeca-, and hexadecasaccharide fragments, was measured by ELISA. Outbred 6-week-old female mice were injected s.c. three times at biweekly intervals with 2.5 g of saccharide as a conjugate and were bled 7 days after the second and third injections. Excepting the tetramer, conjugates of the octamer, dodecamer and hexadecamer elicited IgG LPS antibodies after the second injection, a statistically significant rise (booster) after the third injection, and higher levels than those vaccinated with O-SP-HSA (P ‫؍‬ 0.0001). The highest geometric mean levels of IgG anti-LPS were elicited by the hexadecamer with 9 chains or 9 moles of saccharide͞HSA (15.5 ELISA units) followed by the octamer with 20 chains (11.1 ELISA units) and the dodecamer with 10 chains (9.52 ELISA units). Clinical evaluation of these synthetic saccharides bound to a medically useful carrier is planned.

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Section: Resultsmentioning

confidence: 86%

Protein conjugates of synthetic saccharides elicit higher levels of serum IgG lipopolysaccharide antibodies in mice than do those of the O-specific polysaccharide fromShigella dysenteriaetype 1

Pozsgay

Chu

Pannell

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

169

128

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“…Since C-Ps by itself is a poor systemic immunogen (29), protein conjugates of PCho or C-Ps were used (29, 47, 53). Evidence of on May 11, 2018 by guest http://iai.asm.org/ protection was found in some studies (for example, references 48 and 53).…”

Section: Discussionmentioning

confidence: 99%

“…Pneumococcal cell wall polysaccharide (C-Ps), a ribitol teichoic acid linked to the muramic residues of the cell wall peptidoglycan (9), and the membrane-bound lipoteichoic acid (LTA), consisting of the identical teichoic acid with a glycolipid end group (13), are much-studied species antigens. Natural antibody to the phosphorylcholine (PCho) determinant of pneumococcal teichoic acid was reported in 1981 to be protective in mice (8), and accordingly, the elicitation of antibodies with protein-coupled C-Ps or PCho as a species vaccine has been explored (29,47,48,53). Protection was found in some model systems; in others, however, C-Ps or PCho antibodies were reported to be nonprotective (38,39,47), a result attributed to exclusion by the capsular PS (45).…”

mentioning

confidence: 99%

Antibody-Independent, Interleukin-17A-Mediated, Cross-Serotype Immunity to Pneumococci in Mice Immunized Intranasally with the Cell Wall Polysaccharide

et al. 2006

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Serotype-specific immunity to Streptococcus pneumoniae is conferred by antibodies to the capsular polysaccharides, which define the 90 known serotypes. Whether antibody to the species-common cell wall polysaccharide (C-Ps) is protective has been a matter of controversy. Here we show that C-Ps given intranasally with mucosal adjuvant increased the resistance of mice to experimental nasopharyngeal colonization by capsulated S. pneumoniae of serotype 6B. This immunity could be induced in mice congenitally lacking immunoglobulin but was dependent upon CD4 ؉ T cells. Elimination of the charged amino group on the polymer backbone by N acetylation of C-Ps reduced the immunity, as did treatment of the mice with antibody to the cytokine interleukin-17A at the time of challenge, both consistent with the hypothesis of T-cell activation due to the zwitterionic motif of the polymer. C-Ps also protected in a model of fatal aspiration pneumonia by heavily capsulated serotype 3. These findings suggest a novel immunization strategy against S. pneumoniae.

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“…Treatment of material with nitrous acid leads to the formation of an anhydromannose residue with a free aldehyde group, suitable for conjugation by reductive amination to the free Nε group of a lysine residue in an appropriate carrier protein (Laferrière et al 1997(Laferrière et al , 1998. The effectiveness of this strategy depends on the nature and substitution pattern of the acetamido sugar.…”

Section: Choice Of Carrier Protein and Conjugation Chemistriesmentioning

confidence: 99%

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

Jones

2005

An. Acad. Bras. Ciênc.

169

117

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Glycoconjugate vaccines, in which a cell surface carbohydrate from a micro-organism is covalently attached to an appropriate carrier protein are proving to be the most effective means to generate protective immune responses to prevent a wide range of diseases. The technology appears to be generic and applicable to a wide range of pathogens, as long as antibodies against surface carbohydrates help protect against infection. Three such vaccines, against Haemophilus influenzae type b, Neisseria meningitidis Group C and seven serotypes of Streptococcus pneumoniae, have already been licensed and many others are in development.This article discusses the rationale for the development and use of glycoconjugate vaccines, the mechanisms by which they elicit T cell-dependent immune responses and the implications of this for vaccine development, the role of physicochemical methods in the characterisation and quality control of these vaccines, and the novel products which are under development.

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The synthesis of Streptococcus pneumoniae polysaccharide-tetanus toxoid conjugates and the effect of chain length on immunogenicity

Cited by 63 publications

References 33 publications

Protein conjugates of synthetic saccharides elicit higher levels of serum IgG lipopolysaccharide antibodies in mice than do those of the O-specific polysaccharide fromShigella dysenteriaetype 1

Protein conjugates of synthetic saccharides elicit higher levels of serum IgG lipopolysaccharide antibodies in mice than do those of the O-specific polysaccharide fromShigella dysenteriaetype 1

Antibody-Independent, Interleukin-17A-Mediated, Cross-Serotype Immunity to Pneumococci in Mice Immunized Intranasally with the Cell Wall Polysaccharide

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

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