title: Improved OMV vaccine against Neisseria meningitidis using genetically engineered strains and a detergent-free purification process.
abstract: The use of detergent-extracted outer membrane vesicles (OMVs) is an established approach for development of a multivalent PorA vaccine against N. meningitidis serogroup B. Selective removal of lipopolysaccharide (LPS) decreases toxicity, but promotes aggregation and narrows the immune response. Detergent-free OMV vaccines retain all LPS, which preserves the native vesicle structure, but result in high toxicity and lower yield. The present study assessed the effects of gene mutations that attenuated LPS toxicity (lpxL1) or improved OMV yield (rmpM) in combination with the available OMV purification processes. The results substantiate that OMVs from a strain with both mutations, produced with a detergent-free process provide better vaccine characteristics than the traditional detergent-based approach. With comparable toxicity and yield, no aggregation and cross-protection against other PorA subtypes, these OMV vaccines are potentially safe and effective for parenteral use in humans.
authors.affiliation: Netherlands Vaccine Institute, Unit Research and Development, The Netherlands. bas.van.de.waterbeemd@nvi-vaccin.nl
authors.forename: Bas
authors.initials: B
authors.lastname: van de Waterbeemd
authors.forename: Mathieu
authors.initials: M
authors.lastname: Streefland
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
authors.forename: Bert
authors.initials: B
authors.lastname: Zomer
authors.forename: Harry
authors.initials: H
authors.lastname: van Dijken
authors.forename: Dirk
authors.initials: D
authors.lastname: Martens
authors.forename: René
authors.initials: R
authors.lastname: Wijffels
authors.forename: Leo
authors.initials: L
authors.lastname: van der Pol
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification*; D005818:Genetic Engineering; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity; D008589:Meningococcal Infections / Q000276:immunology*; D022401:Meningococcal Vaccines / Q000737:chemistry / Q000276:immunology* / Q000633:toxicity; D051379:Mice; D009154:Mutation; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics* / Q000276:immunology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008070:Lipopolysaccharides; D022401:Meningococcal Vaccines