title: Evaluation of recombinant lipidated P2086 protein as a vaccine candidate for group B Neisseria meningitidis in a murine nasal challenge model.
abstract: Neisseria meningitidis is a major causative agent of bacterial meningitis in human beings, especially among young children (</=2 years of age). Prevention of group B meningococcal disease represents a particularly difficult challenge in vaccine development, due to the inadequate immune response elicited against type B capsular polysaccharide. We have established an adult mouse intranasal challenge model for group B N. meningitidis to evaluate potential vaccine candidates through active immunization. Swiss Webster mice were inoculated intranasally with meningococci, and bacteria were recovered from the noses for at least 3 days postchallenge. Iron dextran was required in the bacterial inoculum to ensure sufficient meningococcal recovery from nasal tissue postchallenge. This model has been utilized to evaluate the potential of a recombinant lipidated group B meningococcal outer membrane protein P2086 (rLP2086) as a vaccine candidate. In this study, mice were immunized subcutaneously with purified rLP2086 formulated with or without an attenuated cholera toxin as an adjuvant. The mice were then challenged intranasally with N. meningitidis strain H355 or M982, and the colonization of nasal tissue was determined by quantitative culture 24 h postchallenge. We demonstrated that immunization with rLP2086 significantly reduced nasal colonization of mice challenged with the two different strains of group B N. meningitidis. Mice immunized with rLP2086 produced a strong systemic immunoglobulin G response, and the serum antibodies were cross-reactive with heterologous strains of group B N. meningitidis. The antibodies have functional activity against heterologous N. meningitidis strain, as demonstrated via bactericidal and infant rat protection assays. These results suggest that rLP2086 is a potential vaccine candidate for group B N. meningitidis.
authors.affiliation: Wyeth Research, Pearl River, NY 10965, USA. zhudz@wyeth.com
authors.forename: Duzhang
authors.initials: D
authors.lastname: Zhu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Vicki
authors.initials: V
authors.lastname: Barniak
authors.forename: Liesel
authors.initials: L
authors.lastname: Bernfield
authors.forename: Alan
authors.initials: A
authors.lastname: Howell
authors.forename: Gary
authors.initials: G
authors.lastname: Zlotnick
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D003429:Cross Reactions; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008585:Meningitis, Meningococcal / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D051381:Rats
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; C484699:factor H-binding protein, Neisseria meningitidis