scholarly journals Automated glycan assembly of Streptococcus pneumoniae type 14 capsular polysaccharide fragments

RSC Advances ◽  
2020 ◽  
Vol 10 (40) ◽  
pp. 23668-23674 ◽  
Author(s):  
João Louçano ◽  
Peter Both ◽  
Andrea Marchesi ◽  
Linda del Bino ◽  
Roberto Adamo ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Capsular Polysaccharide ◽  
Building Blocks ◽  
Competitive Elisa ◽  
Automated Synthesis ◽  
Type Iii ◽  
Group B ◽  
Insight Into

A streamlined automated synthesis for S. pneumoniae type 14 and Group B Streptococcus type III capsular oligosaccharides with only one set of three building blocks is presented. Competitive ELISA provides some insight into minimal epitope.

scholarly journals Type III Group B Streptococcal Polysaccharide Induces Antibodies That Cross-React with Streptococcus pneumoniae Type 14

2002 ◽  
Vol 70 (4) ◽  
pp. 1724-1738 ◽  
Author(s):  
Hilde-Kari Guttormsen ◽  
Carol J. Baker ◽  
Moon H. Nahm ◽  
Lawrence C. Paoletti ◽  
Susu M. Zughaier ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Bacterial Infections ◽  
Capsular Polysaccharide ◽  
Sialic Acid Residue ◽  
Coating Antigen ◽  
Type Iii ◽  
Young Infants ◽  
Covalently Linked ◽  
Group B

ABSTRACT Covalent linkage of a bacterial polysaccharide to a protein greatly enhances the carbohydrate's immunogenicity and its binding to solid surfaces in immunoassays. These findings have spurred the development of glycoconjugate vaccines to prevent serious bacterial infections as well as the use of glycoconjugates as coating antigens in bioassays. We evaluated sera from women immunized with unconjugated group B streptococcal (GBS) type III (GBS III) polysaccharide (IIIPS) or with IIIPS covalently linked to tetanus toxoid to assess specificity, sensitivity, and parallelism in dilution curves in two GBS III enzyme-linked immunosorbent assays (ELISAs). One assay used IIIPS mixed with methylated human serum albumin (IIIPS + mHSA) as the coating antigen, and the other used IIIPS covalently linked to HSA (III-HSA). Each coating antigen was associated with a highly specific GBS III bioassay. The sensitivity was higher in the III-HSA ELISA, in which conjugated IIIPS is bound to the plates. Parallelism in titration curves was observed in the III-HSA but not in the IIIPS + mHSA ELISA. The excellent correlation between the concentrations of GBS IIIPS-specific immunoglobulin G (IgG) and the opsonophagocytic activity of these antibodies indicated that the III-HSA assay can predict functionality of vaccine-induced IgG against GBS III disease. The structure of the repeating unit of the capsular polysaccharide of GBS III differs from that of Streptococcus pneumoniae type 14 (Pn14 PS) only by the presence on GBS III of a sialic acid residue at the end of the side chain. The majority of healthy adults responding to GBS III vaccines with a fourfold or greater increase in GBS III-specific IgG antibodies developed antibodies cross-reacting with Pn14 PS (i.e., desialylated GBS IIIPS). The proportion of GBS vaccine responders who developed IgG to the desialylated IIIPS did not depend on whether IIIPS was given in the unconjugated or conjugated form. When present, these vaccine-induced cross-reacting antibodies conferred in vitro antibody-mediated opsonophagocytosis and killing of both GBS III and Pn14, two pathogens that cause invasive disease in young infants.

Initial Studies of the Molecular Basis of Peptide Mimicry of Group B Streptococcal Type III Capsular Polysaccharide

2001 ◽  
Vol 20 (2) ◽  
pp. 221-227 ◽  
Author(s):  
Seth H. Pincus ◽  
Stephen R. Lepage ◽  
Robert F. Jung ◽  
Jennifer G. Massey ◽  
Mahesh Jaseja
Keyword(s):  
Molecular Basis ◽  
Capsular Polysaccharide ◽  
Type Iii ◽  
Peptide Mimicry ◽  
Group B

Group B Streptococcal and Pneumococcal Sepsis in Newborn Infants: The Role of Pneumococcal Antibody

PEDIATRICS ◽  
1978 ◽  
Vol 62 (4) ◽  
pp. 620-621
Author(s):  
Gerald W. Fischer ◽  
James W. Bass ◽  
George H. Lowell ◽  
Martin H. Crumrine
Keyword(s):  
Streptococcus Pneumoniae ◽  
Hydrochloric Acid ◽  
Group B Streptococcus ◽  
Newborn Infants ◽  
Polysaccharide Antigen ◽  
Type Iii ◽  
Pneumococcal Sepsis ◽  
Group B

The article by Bortolussi et al. on pneumococcal septicemia and meningitis in the neonat (Pediatrics 60:352, September 1977) was of great interest to us, since we have been analyzing the effect of antibody directed against Streptococcus pneumoniae on group B Streptococcus type III. We have recently shown (unpublished data) that antibody directed against S. pneumoniae type 14 precipitates the hot hydrochloric acid-extracted polysaccharide antigen of group B Streptococcus type III. Further studies have shown that this antibody is opsonic for group B Streptococcus type III in an in vitro bactericidal assay and protective in a suckling rat model of group B Streptococcus type III sepsis.1

Synthesis of a hexasaccharide fragment of the capsular polysaccharide of Streptococcus pneumoniae type 3

2002 ◽  
Vol 80 (1) ◽  
pp. 76-81 ◽  
Author(s):  
Dirk J Lefeber ◽  
Eneko Aldaba Arévalo ◽  
Johannis P Kamerling ◽  
Johannes FG Vliegenthart
Keyword(s):  
Streptococcus Pneumoniae ◽  
Key Words ◽  
Selective Oxidation ◽  
Capsular Polysaccharide ◽  
Building Blocks ◽  
Oligosaccharide Synthesis ◽  
Tempo Oxidation ◽  
Carboxylic Groups ◽  
New Generation ◽  
Type 3

In the framework of the development of a new generation of neoglycoconjugate vaccines against Streptococcus pneumoniae, the synthesis is described of a spacer-containing hexasaccharide fragment related to the capsular polysaccharide of S. pneumoniae type 3. Hexasaccharide β-D-GlcpA-(1[Formula: see text]4)-β-D-Glcp-(1[Formula: see text]3)-β-D-GlcpA-(1[Formula: see text]4)-β-D- Glcp-(1[Formula: see text]3)-β-D-GlcpA-(1[Formula: see text]4)-β-D-Glcp-(1[Formula: see text]O-(CH2)3NH2) (1), comprised of three repeating units, was synthesized via a blockwise strategy employing suitably protected disaccharide building blocks. Carboxylic groups were introduced by selective oxidation with TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) in the last reaction steps. Deprotection afforded target hexasaccharide 1.Key words: oligosaccharide synthesis, Streptococcus pneumoniae type 3, TEMPO oxidation.

scholarly journals Demonstration of opsonic activity and in vivo protection against group B streptococci type III by Streptococcus pneumoniae type 14 antisera.

1978 ◽  
Vol 148 (3) ◽  
pp. 776-786 ◽  
Author(s):  
G W Fischer ◽  
G H Lowell ◽  
M H Crumrine ◽  
J W Bass
Keyword(s):  
Streptococcus Pneumoniae ◽  
Rat Model ◽  
In Vivo Studies ◽  
Group B Streptococci ◽  
Opsonic Activity ◽  
Type Iii ◽  
Neonatal Group ◽  
Group B ◽  
Type 3

The present studies demonstrate that antisera directed against Streptococcus pneumoniae type 14 is opsonic for group B streptococci type III in a neutrophile-mediated bactericidal assay. Specificity was demonstrated by the observations that group B streptococci type III and S. pneumoniae type 14 adsorbed the opsonic activity of anti-S. pneumoniae type 14 antisera. Group B streptococci strain 090R (devoid of type antigens) and S. pneumoniae type 3, did not remove the opsonic activity of anti-S. pneumoniae type 14 serum. In vivo studies using a suckling rat model of neonatal group B streptococcal type III sepsis demonstrated that antisera directed against S. pneumoniae type 14 was highly protective.

scholarly journals Structural Properties of Group B Streptococcal Type III Polysaccharide Conjugate Vaccines That Influence Immunogenicity and Efficacy

1998 ◽  
Vol 66 (5) ◽  
pp. 2186-2192 ◽  
Author(s):  
Michael R. Wessels ◽  
Lawrence C. Paoletti ◽  
Hilde-Kari Guttormsen ◽  
Francis Michon ◽  
Anello J. D’Ambra ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Protective Efficacy ◽  
Molecular Size ◽  
Cross Linking ◽  
Opsonic Activity ◽  
Conjugate Vaccines ◽  
Type Iii ◽  
Protein Conjugate ◽  
Group B ◽  
Protein Cross Linking

ABSTRACT In this study, we tested the hypothesis that the immunogenicity and protective efficacy of polysaccharide-protein conjugate vaccines are influenced by three variables: (i) molecular size of the conjugate, (ii) molecular size of the polysaccharide used for conjugation, and (iii) extent of polysaccharide-to-protein cross-linking. Type III group B Streptococcus capsular polysaccharide was linked by reductive amination at multiple sites to tetanus toxoid to create a polysaccharide-protein conjugate (III-TT). A single lot of III-TT was fractionated into small, medium, and large M rpools. Whereas all three conferred protection in a maternal immunization-neonatal challenge model in mice, the smallestM r conjugate evoked less polysaccharide-specific immunoglobulin G (IgG) than the two largerM r conjugates. To test whether the molecular size of the polysaccharide used for conjugation also affected the immunogenicity of the conjugate, vaccines were synthesized using capsular polysaccharides with M rs of 38,000, 105,000, and 349,000. Polysaccharide-specific IgG responses in mice increased with the M r of the polysaccharides, and protective efficacy was lower for the smallest polysaccharide conjugate compared to the other two vaccines. Immunogenicity testing of a series of vaccines prepared with different degrees of polysaccharide-to-protein cross-linking demonstrated higher polysaccharide-specific antibody responses as the extent of cross-linking increased. However, opsonic activity was greatest in mouse antiserum raised to a moderately cross-linked conjugate, suggesting that some antibodies evoked by highly cross-linked conjugates were directed to a nonprotective epitope. We conclude that conjugate size, polysaccharide size, and degree of polysaccharide-protein cross-linking influence the immunogenicity and protective efficacy of III-TT conjugate vaccines.

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