Improved production process for native outer membrane vesicle vaccine against Neisseria meningitidis

• Published in: PloS one 2013-05, Vol.8 (5), p.e65157-e65157
• Main Authors: van de Waterbeemd, Bas, Zomer, Gijsbert, Kaaijk, Patricia, Ruiterkamp, Nicole, Wijffels, René H, van den Dobbelsteen, Germie P J M, van der Pol, Leo A
• Format: Article
• Language: English
• Subjects: acellular vaccine; adverse events; Animals; Antigens; b meningococcal disease; Bacterial Outer Membrane Proteins - immunology; Batch Cell Culture Techniques - methods; Biology; Bioreactors; Chelating agents; continuous centrifugation; Deactivation; Deoxyribonucleic acid; Developmental stages; DNA; E coli; Engineering; Escherichia coli; Fatty acids; Humans; immunogenicity; Inactivation; Medicine; Membrane vesicles; Meningococcal Vaccines - biosynthesis; Meningococcal Vaccines - isolation & purification; Meningococcal Vaccines - standards; Mice; Neisseria meningitidis; Neisseria meningitidis - immunology; pertussis; Phenols; Porins - immunology; Preservatives; protein; Proteins; Public health; Quality Control; Rabbits; safety; strains; Ultracentrifugation; Vaccines; Whooping cough
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0065157

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.