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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 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.

Original publication

DOI

10.1073/pnas.1314476110

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

19/11/2013

Volume

110

Pages

19077 - 19082

Keywords

Africa South of the Sahara, Animals, Disease Outbreaks, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Glycoconjugates, Humans, Magnetic Resonance Spectroscopy, Meningitis, Meningococcal, Meningococcal Vaccines, Mice, Neisseria meningitidis, Polysaccharides, Bacterial