Micoli, Francesca, Romano, Maria Rosaria, Tontini, Marta, Cappelletti, Emilia, Gavini, Massimiliano, Proietti, Daniela, Rondini, Simona, Swennen, Erwin Frans, Santini, Laura, Filippini, Sara, Balocchi, Cristiana, Adamo, Roberto, Pluschke, Gert, Norheim, Gunnstein, Pollard, Andrew J., Saul, Allan James, Rappuoli, Rino, Maclennan, Calman Alexander, Berti, Francesco and Costantino, Paolo (2013) The development of a glycoconjugate vaccine to prevent meningitis in Africa caused by meningococcal serogroup X. Proceedings of the National Academy of Sciences (PNAS).

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 years. Currently no vaccine is available against MenX. Since 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, after the recent introduction of a glycoconjugate vaccine against serogroup A.
Here we report, for the first time, 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 different 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 an African MenX isolate. These findings support the further development of glycoconjugate vaccines against MenX and their assessment in clinical trials in order to produce a vaccine against the one cause of epidemic meningococcal meningitis that currently cannot be prevented by available vaccines.

Item Type:	Article
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/10094