title: Improved production process for native outer membrane vesicle vaccine against Neisseria meningitidis.
abstract: An improved detergent-free process has been developed to produce vaccine based on native outer membrane vesicles (NOMV) against Neisseria meningitidis serogroup B. Performance was evaluated with the NonaMen vaccine concept, which provides broad coverage based on nine distinct PorA antigens. Scalable aseptic equipment was implemented, replacing undesirable steps like ultracentrifugation, inactivation with phenol, and the use of preservatives. The resulting process is more consistent and gives a higher yield than published reference processes, enabling NOMV production at commercial scale. Product quality met preliminary specifications for 9 consecutive batches, and an ongoing study confirmed real-time stability up to 12 months after production. As the NOMV had low endotoxic activity and induced high bactericidal titres in mice, they are expected to be safe and effective in humans. The production process is not limited to NonaMen and may be applicable for other N. meningitidis serogroups and other gram-negative pathogens. The current results therefore facilitate the late-stage development and clinical evaluation of NOMV vaccines.
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Vaccinology, Bilthoven, The Netherlands. bas.van.de.waterbeemd@intravacc.nl
authors.forename: Bas
authors.initials: B
authors.lastname: van de Waterbeemd
authors.forename: Gijsbert
authors.initials: G
authors.lastname: Zomer
authors.forename: Patricia
authors.initials: P
authors.lastname: Kaaijk
authors.forename: Nicole
authors.initials: N
authors.lastname: Ruiterkamp
authors.forename: René H
authors.initials: RH
authors.lastname: Wijffels
authors.forename: Germie P J M
authors.initials: GP
authors.lastname: van den Dobbelsteen
authors.forename: Leo A
authors.initials: LA
authors.lastname: van der Pol
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D061249:Batch Cell Culture Techniques / Q000379:methods; D019149:Bioreactors; D006801:Humans; D022401:Meningococcal Vaccines / Q000096:biosynthesis* / Q000302:isolation & purification / Q000592:standards; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology*; D018272:Porins / Q000276:immunology; D011786:Quality Control; D011817:Rabbits
chemical_list: D001425:Bacterial Outer Membrane Proteins; D022401:Meningococcal Vaccines; D018272:Porins; C057699:porin protein, Neisseria