scholarly journals A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jacopo Enotarpi ◽  
Marta Tontini ◽  
Cristiana Balocchi ◽  
Daan van der Es ◽  
Ludovic Auberger ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Shelf Life ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Antibody Binding ◽  
Liquid Formulation ◽  
In Vivo Testing ◽  
Protective Antibodies ◽  
Polyclonal Serum

AbstractNeisseria meningitidis serogroup A capsular polysaccharide (MenA CPS) consists of (1 → 6)-2-acetamido-2-deoxy-α-D-mannopyranosyl phosphate repeating units, O-acetylated at position C3 or C4. Glycomimetics appear attractive to overcome the CPS intrinsic lability in physiological media, due to cleavage of the phosphodiester bridge, and to develop a stable vaccine with longer shelf life in liquid formulation. Here, we generate a series of non-acetylated carbaMenA oligomers which are proven more stable than the CPS. An octamer (DP8) inhibits the binding of a MenA specific bactericidal mAb and polyclonal serum to the CPS, and is selected for further in vivo testing. However, its CRM197 conjugate raises murine antibodies towards the non-acetylated CPS backbone, but not the natural acetylated form. Accordingly, random O-acetylation of the DP8 is performed, resulting in a structure (Ac-carbaMenA) showing improved inhibition of anti-MenA CPS antibody binding and, after conjugation to CRM197, eliciting anti-MenA protective murine antibodies, comparably to the vaccine benchmark.

scholarly journals Publisher Correction: A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jacopo Enotarpi ◽  
Marta Tontini ◽  
Cristiana Balocchi ◽  
Daan van der Es ◽  
Ludovic Auberger ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Conjugate Vaccine ◽  
Protective Antibodies

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20120-4

scholarly journals Effect of O Acetylation of Neisseria meningitidis Serogroup A Capsular Polysaccharide on Development of Functional Immune Responses

2002 ◽  
Vol 70 (7) ◽  
pp. 3707-3713 ◽  
Author(s):  
David S. Berry ◽  
Freyja Lynn ◽  
Che-Hung Lee ◽  
Carl E. Frasch ◽  
Margaret C. Bash
Keyword(s):  
Immune Responses ◽  
Neisseria Meningitidis ◽  
Conjugate Vaccine ◽  
Essential Role ◽  
Capsular Polysaccharide ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dramatic Reduction ◽  
Mouse Immunization ◽  
Human Sera ◽  
Inhibition Studies

ABSTRACT The importance of O-acetyl groups to the immunogenicity of Neisseria meningitidis serogroup A polysaccharide (PS) was examined in studies using human sera and mouse immunization. In 17 of 18 postimmunization human sera, inhibition enzyme-linked immunosorbent assay indicated that the majority of antibodies binding to serogroup A PS were specific for epitopes involving O-acetyl groups. Studies with mice also showed an essential role for O-acetyl groups, where serum bactericidal titers following immunization with de-O-acetylated (de-O-Ac) conjugate vaccine were at least 32-fold lower than those following immunization with O-Ac PS-conjugate vaccine and 4-fold lower than those following immunization with native capsular PS. Inhibition studies using native and de-O-Ac PS confirmed the specificity of murine antibodies to native PS. The dramatic reduction in immunogenicity associated with removal of O-acetyl groups indicates that O acetylation is essential to the immunogenic epitopes of serogroup A PS. Since levels of bactericidal antibodies are correlated with protection against disease, O-acetyl groups appear to be important in protection.

scholarly journals Capsular Polysaccharide-Fimbrial Protein Conjugate Vaccine Protects against Porphyromonas gingivalis Infection in SCID Mice Reconstituted with Human Peripheral Blood Lymphocytes

1998 ◽  
Vol 66 (1) ◽  
pp. 391-393 ◽  
Author(s):  
Jeom-Il Choi ◽  
Robert E. Schifferle ◽  
Fuminobu Yoshimura ◽  
Byung-Woo Kim
Keyword(s):  
Conjugate Vaccine ◽  
Porphyromonas Gingivalis ◽  
Capsular Polysaccharide ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Scid Mice ◽  
Protein Conjugate ◽  
Periodontal Infection ◽  
Fimbrial Protein

ABSTRACT The effect of immunization with either a Porphyromonas gingivalis fimbrial protein, a capsular polysaccharide, or a capsular polysaccharide-fimbrial protein conjugate vaccine were compared in hu-PBL-SCID mice. A significantly higher human immunoglobulin G antibody response and the highest degree of in vivo protection against bacterial challenge was observed in the group immunized with the conjugate vaccine. It was concluded that capsular polysaccharide-fimbrial protein conjugate from P. gingivalis could potentially be developed as a vaccine against periodontal infection by P. gingivalis.

scholarly journals Cellular and molecular biology of Neisseria meningitidis colonization and invasive disease

2010 ◽  
Vol 118 (9) ◽  
pp. 547-564 ◽  
Author(s):  
Darryl J. Hill ◽  
Natalie J. Griffiths ◽  
Elena Borodina ◽  
Mumtaz Virji
Keyword(s):  
Respiratory Tract ◽  
Neisseria Meningitidis ◽  
Capsular Polysaccharide ◽  
Antigenic Variation ◽  
Rapid Onset ◽  
Host Cells ◽  
Bacterial Survival ◽  
Human Respiratory Tract ◽  
Adhesive Proteins

The human species is the only natural host of Neisseria meningitidis, an important cause of bacterial meningitis globally, and, despite its association with devastating diseases, N. meningitidis is a commensal organism found frequently in the respiratory tract of healthy individuals. To date, antibiotic resistance is relatively uncommon in N. meningitidis isolates but, due to the rapid onset of disease in susceptible hosts, the mortality rate remains approx. 10%. Additionally, patients who survive meningococcal disease often endure numerous debilitating sequelae. N. meningitidis strains are classified primarily into serogroups based on the type of polysaccharide capsule expressed. In total, 13 serogroups have been described; however, the majority of disease is caused by strains belonging to one of only five serogroups. Although vaccines have been developed against some of these, a universal meningococcal vaccine remains a challenge due to successful immune evasion strategies of the organism, including mimicry of host structures as well as frequent antigenic variation. N. meningitidis express a range of virulence factors including capsular polysaccharide, lipopolysaccharide and a number of surface-expressed adhesive proteins. Variation of these surface structures is necessary for meningococci to evade killing by host defence mechanisms. Nonetheless, adhesion to host cells and tissues needs to be maintained to enable colonization and ensure bacterial survival in the niche. The aims of the present review are to provide a brief outline of meningococcal carriage, disease and burden to society. With this background, we discuss several bacterial strategies that may enable its survival in the human respiratory tract during colonization and in the blood during infection. We also examine several known meningococcal adhesion mechanisms and conclude with a section on the potential processes that may operate in vivo as meningococci progress from the respiratory niche through the blood to reach the central nervous system.

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 Avidity of the Immunoglobulin G Response to a Neisseria meningitidis Group C Polysaccharide Conjugate Vaccine as Measured by Inhibition and Chaotropic Enzyme-Linked Immunosorbent Assays

2007 ◽  
Vol 14 (4) ◽  
pp. 397-403 ◽  
Author(s):  
Shannon L. Harris ◽  
How Tsao ◽  
Lindsey Ashton ◽  
David Goldblatt ◽  
Philip Fernsten
Keyword(s):  
Neisseria Meningitidis ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Enzyme Linked Immunosorbent Assay ◽  
Primary Immunization ◽  
Individual Subject ◽  
Antibody Avidity ◽  
Booster Immunization ◽  
Immunization Series

ABSTRACT Antibody avidity, the strength of the multivalent interaction between antibodies and their antigens, is an important characteristic of protective immune responses. We have developed an inhibition enzyme-linked immunosorbent assay (ELISA) to measure antibody avidity for the capsular polysaccharide (PS) of Neisseria meningitidis group C (MnC) and determined the avidity constants (KD s) for 100 sera from children immunized with an MnC PS conjugate vaccine. The avidity constants were compared to the avidity indices (AI) obtained for the same sera using a chaotropic ELISA protocol. After the primary immunization series, the geometric mean (GM) KD was 674 nM and did not change in the months following immunization. However, the GM avidity did increase after the booster dose (GM KD , 414 nM 1 month after booster immunization). In contrast, the GM AI increased from an initial value of 118 after the primary immunization series to 147 6 months after the completion of the primary immunization series and then further increased to 178 after booster immunization. At the individual subject level, the avidity constant and AI correlated after the primary immunization series and after booster immunization but not prior to boosting. This work suggests that the AI, as measured by the chaotropic ELISA, in contrast to the KD , reflects changes that render antibody populations less susceptible to disruption by chaotropic agents without directly affecting the strength of the binding interactions.

scholarly journals Development and Evaluation of a Dipstick Diagnostic Test for Neisseria meningitidis Serogroup X

2014 ◽  
Vol 53 (2) ◽  
pp. 449-454 ◽  
Author(s):  
Alain Agnememel ◽  
François Traincard ◽  
Sylvie Dartevelle ◽  
Laurence Mulard ◽  
Ali Elhaji Mahamane ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Diagnostic Test ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Positive Likelihood Ratio ◽  
Epidemiological Surveillance ◽  
Diagnostic Tools ◽  
Specific Test ◽  
Content Type ◽  
Meningitis Belt

The emergence ofNeisseria meningitidisserogroup X (NmX) in the African meningitis belt has urged the development of diagnostic tools and vaccines for this serogroup, especially following the introduction of a conjugate vaccine againstN. meningitidisserogroup A (NmA). We have developed and evaluated a new rapid diagnostic test (RDT) for detecting the capsular polysaccharide (cps) antigen of this emerging serogroup. Whole inactivated NmX bacteria were used to immunize rabbits. Following purification by affinity chromatography, the cpsX-specific IgG antibodies were utilized to develop an NmX-specific immunochromatography dipstick RDT. The test was validated against purified cpsX and meningococcal strains of different serogroups. Its performance was evaluated against that of PCR on a collection of 369 cerebrospinal fluid (CSF) samples obtained from patients living in countries within the meningitis belt (Cameroon, Côte d'Ivoire, and Niger) or in France. The RDT was highly specific for NmX strains. Cutoffs of 105CFU/ml and 1 ng/ml were observed for the reference NmX strain and purified cpsX, respectively. Sensitivity and specificity were 100% and 94%, respectively. A high agreement between PCR and RDT (Kappa coefficient, 0.98) was observed. The RDT gave a high positive likelihood ratio and a low negative likelihood (0.07), indicating almost 100% probability of declaring disease or not when the test is positive or negative, respectively. This unique NmX-specific test could be added to the available set of RDT for the detection of meningococcal meningitis in Africa as a major tool to reinforce epidemiological surveillance after the introduction of the NmA conjugate vaccine.

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