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Research Paper
Characterization of the key antigenic components and pre-clinical immune responses to a meningococcal disease vaccine based on Neisseria lactamica outer membrane vesicles
Michelle Finney, Thomas Vaughan, Stephen Taylor, Michael J. Hudson, Catherine Pratt, Jun X. Wheeler, Caroline Vipond, Ian Feavers, Christopher Jones, Jamie Findlow, Ray Borrow and Andrew Gorringe
volume 4 | issue 1
january/february 2008Pages: 23 - 30
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Serogroup B strains are now responsible for over 80% of meningococcal disease in the UK and no suitable vaccine is available that confers universal protection against all serogroup B strains. Neisseria lactamica shares many antigens with the meningococcus, except capsule and the surface protein PorA. Many of these antigens are thought to be responsible for providing cross-protective immunity to meningococcal disease. We have developed an N. lactamica vaccine using methods developed for meningococcal outer membrane vesicle (OMV) vaccines. The major antigenic components were identified by excision of 11 major protein bands from an SDS-PAGE gel, followed by mass spectrometric identification. These bands contained at least 22 proteins identified from an unassembled N. lactamica genome, 15 of which having orthologues in published pathogenic Neisseria genomes. Western blotting revealed that most of these bands were immunogenic, and antibodies to these proteins generally cross-reacted with N. meningitidis proteins. Sera from mice and rabbits immunised with either N. lactamica or N. meningitidis OMVs produced comparable cross-reactive ELISA titres against OMVs prepared from a panel of diverse meningococcal strains. Mice immunised with either N. meningitidis or N. lactamica OMVs showed no detectable serum bactericidal activity against the panel of target strains except N. meningitidis OMV sera against the homologous strain. Similarly, rabbit antisera to N. lactamica OMVs elicited little or no bactericidal antibodies against the panel of serogroup B meningococcal strains. However, such antisera did mediate opsonophagocytosis, suggesting that this may be a mechanism by which this vaccine protects in a mouse model of meningococcal bacteraemia.
Authors
Michelle Finney
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, United Kingdom
Thomas Vaughan
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, United Kingdom
Stephen Taylor
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, United Kingdom
Michael J. Hudson
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, United Kingdom
Catherine Pratt
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, United Kingdom
Jun X. Wheeler
National Institute for Biological Standards and Control, South Mimms, United Kingdom
Caroline Vipond
National Institute for Biological Standards and Control, South Mimms, United Kingdom
Ian Feavers
National Institute for Biological Standards and Control, South Mimms, United Kingdom
Christopher Jones
National Institute for Biological Standards and Control, South Mimms, United Kingdom
Jamie Findlow
Vaccine Evaluation Unit, Health Protection Agency North West, Manchester Royal Infirmary, Manchester, United Kingdom
Ray Borrow
Vaccine Evaluation Unit, Health Protection Agency North West, Manchester Royal Infirmary, Manchester, United Kingdom
Andrew Gorringe
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, United Kingdom







