Characterization of size, structure and purity of serogroup X Neisseria meningitidis polysaccharide, and development of an assay for quantification of human antibodies

Xie, Ouli; Bolgiano, Barbara; Gao, Fang; Lockyer, Kay; Swann, Carolyn; Jones, Christopher; Delrieu, Isabelle; Njanpop-Lafourcade, Berthe-Marie; Tamekloe, Tsidi Agbeko; Pollard, Andrew J.; Norheim, Gunnstein

doi:10.1016/j.vaccine.2012.07.032

Cited by 28 publications

(19 citation statements)

References 43 publications

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“…The process is scalable and suitable for good manufacturing practice production. Approximately 200 mg of purified MenX PS was obtained from 1 L of fermentation broth, a productivity much higher than previously reported with MenX isolates (9.6-20 mg/L) (31,50,51). Studies on MenX PS and derived OS indicated that they are stable in aqueous solution (31,33), providing the opportunity to develop a fully liquid vaccine formulation with clear advantages in terms of cost and practical utilization compared with freeze-dried formulations that require reconstitution with water.…”

Section: Discussionmentioning

confidence: 72%

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Development of a glycoconjugate vaccine to prevent meningitis in Africa caused by meningococcal serogroup X

Micoli

Romano

Tontini

et al. 2013

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

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Neisseria meningitidis is a major cause of bacterial meningitis worldwide, especially in the African meningitis belt, and has a high associated mortality. The meningococcal serogroups A, W, and X have been responsible for epidemics and almost all cases of meningococcal meningitis in the meningitis belt over the past 12 y. Currently no vaccine is available against meningococcal X (MenX). Because the development of a new vaccine through to licensure takes many years, this leaves Africa vulnerable to new epidemics of MenX meningitis at a time when the epidemiology of meningococcal meningitis on the continent is changing rapidly, following the recent introduction of a glycoconjugate vaccine against serogroup A. Here, we report the development of candidate glycoconjugate vaccines against MenX and preclinical data from their use in animal studies. Following optimization of growth conditions of our seed MenX strain for polysaccharide (PS) production, a scalable purification process was developed yielding high amounts of pure MenX PS. Different glycoconjugates were synthesized by coupling MenX oligosaccharides of varying chain length to CRM 197 as carrier protein. Analytical methods were developed for in-process control and determination of purity and consistency of the vaccines. All conjugates induced high anti-MenX PS IgG titers in mice. Antibodies were strongly bactericidal against African MenX isolates. These findings support the further development of glycoconjugate vaccines against MenX and their assessment in clinical trials to produce a vaccine against the one cause of epidemic meningococcal meningitis that currently cannot be prevented by available vaccines.

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Section: Discussionmentioning

confidence: 72%

“…The structure of MenX PS consists of N-acetylglucosamine-4-phosphate residues held together by α-(1-4) phosphodiester bonds without O-acetyl groups (28,(30)(31)(32)(33).…”

Section: Significancementioning

confidence: 99%

Development of a glycoconjugate vaccine to prevent meningitis in Africa caused by meningococcal serogroup X

Micoli

Romano

Tontini

et al. 2013

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

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“…The yield was about 20 mg/liter of culture. The profile of the purified cpsX was checked by proton nuclear magnetic resonance ( 1 H NMR) (data not shown), as previously described (20). cpsA, cpsB, cpsC, cpsY, and cpsW were similarly purified from five strains of serogroups A, B, C, Y, and W (N. meningitidis strains 21524, 21721, 22639, 16366, and 19995, respectively; Table 1).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2015

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The emergence of Neisseria meningitidis serogroup 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 against N. meningitidis serogroup 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 10 5 CFU/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. N eisseria meningitidis is an exclusively human capsulated bacterium that can provoke severe invasive infections, such as meningitis and septicemia (1). Meningococcal disease is still a major public health concern due to potential epidemic spread. While the disease occurs sporadically in Europe and North America, it is responsible for major recurrent epidemics within the African meningitis belt (2). The bacterial capsular polysaccharide determines the 12 N. meningitidis serogroups currently described. Six serogroups (A, B, C, Y, W, and X) are responsible for the vast majority of cases of meningococcal disease worldwide. However, they differ in their global frequencies and geographical distribution (3). This distribution impacts vaccination strategies, which for the most part involve established polysaccharide-based vaccines against serogroups A, C, Y, and W. Besides, an innovative recombinant protein-based vaccine was recently licensed in Europe and Australia against meningococci of serogroup B (4). This multicomponent vaccine targets conserved proteins among meningococci, regardless of their serogroup. Therefore, it has the potential to cover non-serogroup-B isolates, such as those of serogroup X (5). In the meningitis belt, N. meningitidis serogroup A (NmA) predominated prior to the introduction of the NmA polysaccharide-protein conjugate va...

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“…[4][5][6][7][8] They are high molecular weight antigens with repeating epitopes that are displayed on bacterial and fungal cell surfaces. [9][10][11][12] The B. pseudomallei CPS is comprised of an unbranched homopolymer of 1,3-linked 2-O-acetyl-6-deoxy-b-D-mannoheptopyranose residues. 13 CPS has been shown to inhibit phagocytosis by reducing the amount of complement factor C3b that is deposited on the bacterial cell surface.…”

Section: Introductionmentioning

confidence: 99%

Contribution of murine IgG Fc regions to antibody binding to the capsule ofBurkholderia pseudomallei

et al. 2016

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Characterization of size, structure and purity of serogroup X Neisseria meningitidis polysaccharide, and development of an assay for quantification of human antibodies

Cited by 28 publications

References 43 publications

Development of a glycoconjugate vaccine to prevent meningitis in Africa caused by meningococcal serogroup X

Development of a glycoconjugate vaccine to prevent meningitis in Africa caused by meningococcal serogroup X

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

Contribution of murine IgG Fc regions to antibody binding to the capsule ofBurkholderia pseudomallei

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