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Infection and Immunity, November 2004, p. 6511-6518, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6511-6518.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Expression of Heterologous Antigens in Commensal Neisseria spp.: Preservation of Conformational Epitopes with Vaccine Potential

Clíona A. O'Dwyer,1 Karen Reddin,2 Denis Martin,3 Stephen C. Taylor,2 Andrew R. Gorringe,2 Michael J. Hudson,2 Bernard R. Brodeur,3 Paul R. Langford,1 and J. Simon Kroll1*

Molecular Infectious Diseases Group, Department of Paediatrics, Faculty of Medicine, Imperial College LondonLondon,1 Health Protection Agency, Porton Down, Salisbury, United Kingdom,2 Unité de Recherche en Vaccinologie, Centre Hospitalier Universitaire de Quebec, Ste-Foy, and Shire Biologics Inc., Laval, Quebec, Canada3

Received 26 April 2004/ Returned for modification 18 June 2004/ Accepted 19 July 2004

Commensal neisseriae share with Neisseria meningitidis (meningococcus) a tendency towards overproduction of the bacterial outer envelope, leading to the formation and release during growth of outer membrane vesicles (OMVs). OMVs from both meningococci and commensal neisseriae have shown promise as vaccines to protect against meningococcal disease. We report here the successful expression at high levels of heterologous proteins in commensal neisseriae and the display, in its native conformation, of one meningococcal outer membrane protein vaccine candidate, NspA, in OMVs prepared from such a recombinant Neisseria flavescens strain. These NspA-containing OMVs conferred protection against otherwise lethal intraperitoneal challenge of mice with N. meningitidis serogroup B, and sera raised against them mediated opsonophagocytosis of meningococcal strains expressing this antigen. This development promises to facilitate the design of novel vaccines containing membrane protein antigens that are otherwise difficult to present in native conformation that provide cross-protective efficacy in the prevention of meningococcal disease.

* Corresponding author. Mailing address: Molecular Infectious Diseases Group, Department of Paediatrics, Faculty of Medicine, Imperial College London, and Wright-Fleming Institute, St. Mary's Hospital Campus, London W2 1PG, United Kingdom. Phone: 44 20 7594 3695. Fax: 44 20 7594 3984. E-mail: s.kroll{at}imperial.ac.uk.

Editor: V. J. DiRita

Infection and Immunity, November 2004, p. 6511-6518, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6511-6518.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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