title: Expression of heterologous antigens in commensal Neisseria spp.: preservation of conformational epitopes with vaccine potential.
abstract: 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.
authors.affiliation: Molecular Infectious Diseases Group, Department of Paediatrics, Faculty of Medicine, Imperial College London, UK.
authors.forename: Clíona A
authors.initials: CA
authors.lastname: O'dwyer
authors.forename: Karen
authors.initials: K
authors.lastname: Reddin
authors.forename: Denis
authors.initials: D
authors.lastname: Martin
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Taylor
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gorringe
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hudson
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Brodeur
authors.forename: Paul R
authors.initials: PR
authors.lastname: Langford
authors.forename: J Simon
authors.initials: JS
authors.lastname: Kroll
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology / Q000378:metabolism; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D003227:Conjugation, Genetic; D022162:Cytoplasmic Vesicles; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007116:Immunization, Passive; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009343:Neisseria / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology; D009895:Opsonin Proteins; D010587:Phagocytosis; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D000939:Epitopes; D022401:Meningococcal Vaccines; C105506:NspA protein, Neisseria; D009895:Opsonin Proteins; D011994:Recombinant Proteins