title: The development of a meningococcal disease vaccine based on Neisseria lactamica outer membrane vesicles.
abstract: Serogroup B meningococcal disease remains a serious problem in many countries and no effective vaccine is currently available. Immunological and epidemiological evidence suggests that carriage of commensal Neisseria species is involved in the development of natural immunity against meningococcal disease. Neisseria lactamica has many surface structures in common with Neisseria meningitidis and may be the most important of these species. We have produced extensive pre-clinical data, which indicate that N. lactamica outer membrane vesicles (OMVs) may provide a vaccine effective against diverse disease-causing meningococcal strains. Immunisation with N. lactamica OMVs protected against lethal challenge with diverse meningococcal isolates in a mouse intraperitoneal challenge model of meningococcal disease and we are developing this vaccine for use in a phase I safety and immunogenicity study in adult volunteers. We have shown that OMVs produced from bacteria grown under iron-limited or iron-rich conditions provide equivalent protection in the mouse infection model and thus OMVs produced from iron-rich will be used. Sterile filtration of N. lactamica OMVs has proved difficult but this has been improved by resuspending the vesicles in a buffer, which increases their surface zeta potential. The vaccine is currently being manufactured and validated ELISA protocols have been developed for the analysis of serological responses.
authors.affiliation: Health Protection Agency, Porton Down, Salisbury SP4 0JG, UK. andrew.gorringe@hpa.org.uk
authors.forename: Andrew
authors.initials: A
authors.lastname: Gorringe
authors.forename: Denise
authors.initials: D
authors.lastname: Halliwell
authors.forename: Mary
authors.initials: M
authors.lastname: Matheson
authors.forename: Karen
authors.initials: K
authors.lastname: Reddin
authors.forename: Michelle
authors.initials: M
authors.lastname: Finney
authors.forename: Michael
authors.initials: M
authors.lastname: Hudson
mesh_terms: D000328:Adult; D000818:Animals; D001428:Bacterial Vaccines / Q000302:isolation & purification* / Q000494:pharmacology; D002462:Cell Membrane / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005374:Filtration / Q000379:methods; D006801:Humans; D007114:Immunization; D008589:Meningococcal Infections / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D042806:Neisseria lactamica / Q000276:immunology*; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology; D013242:Sterilization / Q000379:methods
chemical_list: D001428:Bacterial Vaccines