title: Intranasal immunization of mice with recombinant lipidated P2086 protein reduces nasal colonization of group B Neisseria meningitidis.
abstract: Neisseria meningitidis is a major cause of bacterial meningitis in the human population, especially among young children. There is a need to develop a non-capsular vaccine to prevent meningococcal B infections due to the inadequate immune response elicited against the capsular polysaccharide of these strains. Previously, we developed a Swiss Webster adult mouse intranasal challenge model for group B N. meningitidis and evaluated several potential vaccine candidates including a meningococcal outer membrane protein, P2086, through parenteral immunization. Since N. meningitidis is a respiratory pathogen, a mucosal immune response may play an important role in the defense against meningococcal infections. Thus, intranasal immunization may be more effective than traditional parenteral immunization. In this study, mice were immunized intranasally with purified recombinant lipidated P2086 protein (rLP2086) adjuvanted with either CT-E29H, a genetically modified cholera toxin that is significantly reduced in enzymatic activity and toxicity or RC529-AF, a synthetic immunostimulant molecule in aqueous formulation. rLP2086-specific serum and mucosal IgG and IgA antibodies were induced. IgG antibodies reacted with whole cells of multiple strains of group B N.meningitidis. The antibodies have functional activity against N. meningitidis as demonstrated by bactericidal assays. Moreover, immunized mice exhibited reduced nasal colonization of group B meningococcal strains in the intranasal challenge model. These results demonstrate that an intranasal immunization with rLP2086 protein formulated with a detoxified cholera toxin or RC529-AF could prevent the initial colonization of group B meningococcus and become an effective immunization strategy against group B N. meningitidis.
authors.affiliation: Wyeth Vaccines Research, Pearl River, NY 10965, USA. zhudz@wyeth.com
authors.forename: Duzhang
authors.initials: D
authors.lastname: Zhu
authors.forename: Vicki
authors.initials: V
authors.lastname: Barniak
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bruce
authors.initials: B
authors.lastname: Green
authors.forename: Gary
authors.initials: G
authors.lastname: Zlotnick
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000276:immunology*; D002353:Carrier State / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D009666:Nose / Q000276:immunology* / Q000382:microbiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D013047:Specific Pathogen-Free Organisms
chemical_list: D001426:Bacterial Proteins; D007074:Immunoglobulin G; D011994:Recombinant Proteins