scholarly journals A human monoclonal macroglobulin with specificity for alpha(2----8)-linked poly-N-acetyl neuraminic acid, the capsular polysaccharide of group B meningococci and Escherichia coli K1, which crossreacts with polynucleotides and with denatured DNA.

1986 ◽  
Vol 164 (2) ◽  
pp. 642-654 ◽  
Author(s):  
E A Kabat ◽  
K G Nickerson ◽  
J Liao ◽  
L Grossbard ◽  
E F Osserman ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Neuraminic Acid ◽  
Molecular Structures ◽  
Human Pathogens ◽  
E Coli ◽  
Group B ◽  
Antigen Antibody ◽  
Antibody Interactions ◽  
Escherichia Coli K1 ◽  
Horse Antiserum

We have described an IgM antibody from a patient with macroglobulinemia specifically reacting with poly-alpha(2----8)N-acetyl neuraminic acid (NeuNAc) the capsular polysaccharide of two important human pathogens, group B meningococcus and E. coli K1. This antibody has a narrowly defined specificity in its interactions with polysaccharides, being unable to bind poly-alpha(2----9)NeuNAc or alternating poly-alpha(2----8)alpha(2----9)NeuNAc. However, it shows interesting crossreactivity with seemingly unrelated polynucleotides and denatured DNA, supporting the hypothesis that charged groups with a given spacing may determine the specificity of antigen-antibody interactions on otherwise dissimilar molecular structures. Despite the crossreactivity with denatured DNA and polynucleotides, the antibody does not appear to have adverse effects in the patient. The antibody protects newborn rats against E. coli K1 infection, as well as the standard horse antiserum H46, and one would expect it to prove useful in humans as an adjunct to antibiotic therapy in infections with group B meningococcus and E. coli K1. We have attempted to clone the antibody-producing cells from peripheral blood, and have shown that the relevant cells are present and can be cultured.

scholarly journals N-Propionylated Group B Meningococcal Polysaccharide Mimics a Unique Bactericidal Capsular Epitope in Group B Neisseria meningitidis

1997 ◽  
Vol 185 (11) ◽  
pp. 1929-1938 ◽  
Author(s):  
Robert A. Pon ◽  
Michele Lussier ◽  
Qing-Ling Yang ◽  
Harold J. Jennings
Keyword(s):  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Polysialic Acid ◽  
Passive Protection ◽  
E Coli ◽  
High Molecular Weight Form ◽  
Protective Epitope ◽  
Group B ◽  
Molecular Weight Form ◽  
Escherichia Coli K1

The N-propionylated group B meningococcal polysaccharide (NPrGBMP) mimics a unique protective epitope on the surface of group B meningococci (GBM) and Escherichia coli K1. Using a series of monoclonal antibodies (mAbs) induced by the NPrGBMP–monomeric tetanus toxoid (TT) conjugate vaccine it was demonstrated that mAbs having specificities for both extended and conventional short segments of the NPrGBMP were formed, but only the former were bactericidal, and/or gave passive protection against live challenge by GBM. The failure of mAbs specific for short epitopes to protect was further established when (NeuPr)4–TT was used as the vaccine. Of all the mAbs produced that were specific for short internal segments of the NPrGBMP, none were protective, despite the fact that most of them cross-react with the GBM capsular polysaccharide. In contrast, most of the protective mAbs produced by NPrGBMP– TT did not recognize the group B meningococcal polysaccharide (GBMP) unless it was present in its aggregated high molecular weight form. The bactericidal epitope mimicked by the NPrGBMP was shown to be ubiquitous in the capsule of both GBM and E. coli K1 using immunogold labeling techniques and, because of its unique properties, its identification could be significant in the development of a comprehensive conjugate vaccine against group B meningococcal meningitis. This is because most known human α(2–8)-polysialic acid self-antigens can be accommodated in 30–50 α(2–8)-linked sialic acid residues, which is roughly equivalent to an 11-kD length of the GBMP. It has been hypothesized that the formation of the protective epitope on the surface of GBM is due to the interaction of helical segments of the GBMP with another molecule and that the protective epitope is mimicked by the NPrGBMP. Support for the above hypothesis is provided by the fact that the protective NPrGBMP epitope has a similar unusual length dependency to that of the GBMP epitope.

scholarly journals Screening for cross-reacting capsular polysaccharide K antigens of Escherichia coli using antiserum agar

1977 ◽  
Vol 5 (4) ◽  
pp. 490-491
Author(s):  
G W Counts ◽  
M Turck
Keyword(s):  
Escherichia Coli ◽  
Capsular Polysaccharide ◽  
Haemophilus Influenzae Type ◽  
Haemophilus Influenzae Type B ◽  
Type B ◽  
E Coli ◽  
Polysaccharide K ◽  
Polysaccharide Antigens ◽  
Group B ◽  
Escherichia Coli K1

Agar plates containing antiserum against group B meningococcus or Haemophilus influenzae type b were used to determine the prevalence of cross-reacting K1 and K100 capsular polysaccharide antigens in 265 isolates of disease-causing Escherichia coli. K1 antigen was found in 22% of isolates from various sites. K100 antigen was found in only three isolates. This technique is a convenient method to detect specific E. coli K antigens for evaluation as possible factors important in the virulence of the organism.

Serological and conformational properties of E. coli K92 capsular polysaccharide and its N-propionylated derivative both illustrate that induced antibody does not recognize extended epitopes of polysialic acid: Implications for a comprehensive conjugate vaccine against groups B and C N. meningitidis

2002 ◽  
Vol 80 (8) ◽  
pp. 1055-1063 ◽  
Author(s):  
Robert A Pon ◽  
Nam Huan Khieu ◽  
Qing-Ling Yang ◽  
Jean-Robert Brisson ◽  
Harold J Jennings
Keyword(s):  
Molecular Dynamics ◽  
Immune Response ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Competitive Inhibition ◽  
Polysialic Acid ◽  
E Coli ◽  
Protective Epitope ◽  
Conformational Properties ◽  
Group B

The capsular polysaccharide of E. coli K92 (K92P) contains elements in common with the capsular polysaccharides of both groups B and C N. meningitidis, and may therefore form the basis of a bivalent vaccine. In an attempt to augment the cross-protective immune response to group B meningococci, the N-acetyl groups of the K92P were replaced by N-propionyl groups (NPrK92P) and conjugated to protein. This strategy had previously been applied with success to the poorly immunogenic capsular polysaccharide of group B meningococcus (GBMP), and the bactericidal epitope was found to be exclusively mimicked by extended helical segments of the NPrGBMP. The NPrK92P-conjugate, in relation to a K92P-conjugate, failed to enhance the response to GBMP but did generate a measurable response to NPrGBMP, but only at the expense of a greatly reduced GCMP response. Despite the presence of an immune response to NPrGBMP, the anti-NPrK92 serum was not bactericidal. Competitive inhibition studies with NPrGBMP oligosaccharides suggested the NPrK92 antibodies could not cross-react with the protective epitope on group B meningococci, as defined by extended helical segments of the NPrGBMP, but only recognized short non-bactericidal NPrGBMP epitopes. This hypothesis was supported from the conformational and molecular dynamics studies of the K92P, which demonstrated a lack of extended conformations that resemble the GBMP extended epitope. Indeed, the conformational properties of the K92P more closely resembled those of the GCMP, thereby explaining the observed moderate cross-protection of the K92P antiserum towards group C meningococci. Thus, on the basis of these results, it can be concluded that K92P, regardless of N-propionyl modification, will not serve as an effective single vaccine component against both groups B and C meningococci.Key words: conjugate vaccine, Neisseria meningitidis, polysialic acid, NMR, molecular dynamics.

scholarly journals Radioimmunoassay for measuring antibodies specific for group B streptococcal types Ia, Ib, Ic, II, and III

1976 ◽  
Vol 3 (5) ◽  
pp. 480-485
Author(s):  
H W Wilkinson ◽  
W L Jones
Keyword(s):  
Carbohydrate Antigens ◽  
Specific Antibodies ◽  
Type Antigen ◽  
Human Sera ◽  
Group B ◽  
Primary Type ◽  
Antigen Antibody ◽  
Antibody Interactions

The object of this study was to develop a test that would measure antibodies directed against group B streptococcal types Ia, Ib, Ic, II, and III. The type-specific carbohydrate antigens were purified, labeled with 125I, and used to develop a radioimmunoassay. This procedure should be particularly useful in testing human sera for group B type-specific antibodies, since it requires very small quantities of antigens and measures primary type antigen-antibody interactions.

Are antibodies to the capsular polysaccharide of Neisseria meningitidis group B and Escherichia coli K1 associated with immunopathology?

Vaccine ◽  
2006 ◽  
Vol 24 (3) ◽  
pp. 221-228 ◽  
Author(s):  
Daniel M. Stein ◽  
John Robbins ◽  
Mark A. Miller ◽  
Feng-Ying C. Lin ◽  
Rachel Schneerson
Keyword(s):  
Escherichia Coli ◽  
Neisseria Meningitidis ◽  
Capsular Polysaccharide ◽  
Group B ◽  
Escherichia Coli K1

Antibodies to the capsular polysaccharide of Neisseria meningitidis group B or E. coli K1 bind to the brains of infant rats in vitro but not in vivo

1986 ◽  
Vol 1 (1) ◽  
pp. 101-105 ◽  
Author(s):  
Kirsi Saukkonen ◽  
Matti Haltia ◽  
Matthias Frosch ◽  
Dieter Bitter-Süerman ◽  
Maija Leinonen
Keyword(s):  
Neisseria Meningitidis ◽  
Capsular Polysaccharide ◽  
E Coli ◽  
Infant Rats ◽  
Group B

scholarly journals N-acetyl-d-neuraminic acid synthesis in Escherichia coli K1 occurs through condensation of N-acetyl-d-mannosamine and pyruvate

1995 ◽  
Vol 308 (2) ◽  
pp. 501-505 ◽  
Author(s):  
L B Rodríguez-Aparicio ◽  
M A Ferrero ◽  
A Reglero
Keyword(s):  
Escherichia Coli ◽  
Pyruvate Decarboxylase ◽  
Acid Synthesis ◽  
Neuraminic Acid ◽  
Chromatographic Peak ◽  
E Coli ◽  
Crude Extracts ◽  
Lyase Activity ◽  
Escherichia Coli K1

Two enzymes have been found to be involved in bacterial N-acetyl-D-neuraminic acid (NeuAc) synthesis: NeuAc synthase, which condenses N-acetyl-L,D-mannosamine and phosphoenolpyruvate, and NeuAc lyase or NeuAc aldolase, which condenses N-acetyl-D-mannosamine and pyruvate. When we used Escherichia coli K1 crude extracts, we observed the generation of NeuAc in the presence of N-acetylmannosamine and both phosphoenolpyruvate (NeuAc synthase activity) or pyruvate (NeuAc lyase activity). However, when crude extracts were fractionated by Sephacryl S-200 chromatography, NeuAc synthase activity disappeared. A chromatographic peak of NeuAc synthase activity was detected when column fractions were re-tested in the presence of the active NeuAc lyase peak. Furthermore, crude extracts converted phosphoenolpyruvate into pyruvate. Pyruvate depletion, due to the addition of pyruvate decarboxylase to the NeuAc synthase reaction mixture, blocked NeuAc formation. Moreover, after NeuAc lyase immunoprecipitation no NeuAc synthase was detected. These findings suggest that NeuAc synthase is not present in E. coli K1 and therefore that NeuAc lyase is the only enzyme responsible for NeuAc synthesis in this bacterium.

scholarly journals The epitope associated with the binding of the capsular polysaccharide of the group B meningococcus and of Escherichia coli K1 to a human monoclonal macroglobulin, IgMNOV.

1988 ◽  
Vol 168 (2) ◽  
pp. 699-711 ◽  
Author(s):  
E A Kabat ◽  
J Liao ◽  
E F Osserman ◽  
A Gamian ◽  
F Michon ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Maximum Size ◽  
Structural Features ◽  
Unit Weight ◽  
Resonance Spectroscopy ◽  
E Coli ◽  
Effects Of Ph ◽  
Linear Molecules ◽  
The Difference ◽  
Group B

The fine structure of the combining site of human mAb IgMNOV to poly-alpha(2----8)linked NeuNAc, the epitope of the group B meningococcal and E. coli K1 polysaccharides, has been probed using RIA and ELISA. Inhibition by oligomers ranging from 2 to 12 residues was used to assay binding to IgMNOV by group B meningococcal polysaccharide preparations (GBMP) or by poly(A). The inhibitory properties of the oligomers were almost identical in both assays of the binding of GBMP to horse IgM (H46). This evidence and the finding that both GBMP and poly(A) precipitated IgMNOV equally per unit weight indicated that the epitope of poly(A) must mimic an equivalent epitope on GBMP despite the absence of any apparent common structural features in the two molecules. Unlike most carbohydrate-anticarbohydrate systems in which the site is saturated by oligomers of up to six or seven sugars, all the anti-alpha(2----8)NeuNAc systems above required much larger oligomers. Because these oligomers are larger than the maximum size of an antibody site the epitope must be conformationally controlled, and this has been confirmed by nuclear magnetic resonance spectroscopy. However, despite the above similarities, GBMP and poly(A) were differentiated in that only GBMP bound to H46. Smaller linear molecules obtained by delipidating the GBMP, as well as periodate-oxidized GBMP with its nonreducing end oxidized or linked covalently to BSA, bound to and precipitated IgMNOV and H46. This showed that, despite their differences, terminal nonreducing ends were not involved and that both epitopes were located in the conformationally controlled inner residues of the GBMP. The difference thus must reside in the ability of IgMNOV and H46 to recognize different structural aspects of the same conformationally controlled inner residues. The ELISA data indicate that both IgMNOV and H46 have groove-type sites that bind exclusively to an epitope located on the acidic side of the inner residues. The differences determining the ability of IgMNOV and the failure of H46 to cross-react with poly(A), poly(I), and denatured DNA, may depend on differences in the degree of protonation required by each antibody, and this may be clarified by a study of the effects of pH on the precipitin behavior of IgMNOV and H46.

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