title: Development of a glycoconjugate vaccine to prevent meningitis in Africa caused by meningococcal serogroup X.
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.
authors.affiliation: Novartis Vaccines Institute for Global Health, and Research, Novartis Vaccines and Diagnostics, I-53100 Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Micoli
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Romano
authors.forename: Marta
authors.initials: M
authors.lastname: Tontini
authors.forename: Emilia
authors.initials: E
authors.lastname: Cappelletti
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Gavini
authors.forename: Daniela
authors.initials: D
authors.lastname: Proietti
authors.forename: Simona
authors.initials: S
authors.lastname: Rondini
authors.forename: Erwin
authors.initials: E
authors.lastname: Swennen
authors.forename: Laura
authors.initials: L
authors.lastname: Santini
authors.forename: Sara
authors.initials: S
authors.lastname: Filippini
authors.forename: Cristiana
authors.initials: C
authors.lastname: Balocchi
authors.forename: Roberto
authors.initials: R
authors.lastname: Adamo
authors.forename: Gerd
authors.initials: G
authors.lastname: Pluschke
authors.forename: Gunnstein
authors.initials: G
authors.lastname: Norheim
authors.forename: Andrew
authors.initials: A
authors.lastname: Pollard
authors.forename: Allan
authors.initials: A
authors.lastname: Saul
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Calman A
authors.initials: CA
authors.lastname: MacLennan
authors.forename: Francesco
authors.initials: F
authors.lastname: Berti
authors.forename: Paolo
authors.initials: P
authors.lastname: Costantino
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D000818:Animals; D004196:Disease Outbreaks / Q000517:prevention & control*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006001:Glycoconjugates / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008585:Meningitis, Meningococcal / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D009345:Neisseria meningitidis / Q000235:genetics* / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D006001:Glycoconjugates; D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial