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

Micoli, Francesca and Romano, Maria Rosaria and Tontini, Marta and Cappelletti, Emilia and Gavini, Massimiliano and Proietti, Daniela and Rondini, Simona and Swennen, Erwin and Santini, Laura and Filippini, Sara and Balocchi, Cristiana and Adamo, Roberto and Pluschke, Gerd and Norheim, Gunnstein and Pollard, Andrew and Saul, Allan and Rappuoli, Rino and Maclennan, Calman A. and Berti, Francesco and Costantino, Paolo. (2013) Development of a glycoconjugate vaccine to prevent meningitis in Africa caused by meningococcal serogroup X. Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, H. 47. pp. 19077-19082.

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Official URL: http://edoc.unibas.ch/dok/A6211919

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Abstract

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 CRM197 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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Molecular Immunology (Pluschke)
UniBasel Contributors:Pluschke, Gerd
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:National Academy of Sciences
ISSN:0027-8424
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:23 May 2014 08:34
Deposited On:23 May 2014 08:34

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