title: Bordetella pertussis fimbriae are effective carrier proteins in Neisseria meningitidis serogroup C conjugate vaccines.
abstract: Serogroup C meningococcal conjugate vaccines generally use diphtheria or tetanus toxoids as the protein carriers. The use of alternative carrier proteins may allow multivalent conjugate vaccines to be formulated into a single injection and circumvent potential problems of immune suppression in primed individuals. Bordetella pertussis fimbriae were assessed as carrier proteins for Neisseria meningitidis serogroup C polysaccharide. Fimbriae were conjugated to the polysaccharide using modifications of published methods and characterised by size exclusion chromatography; co-elution of protein and polysaccharide moieties confirmed conjugation. The conjugates elicited boostable IgG responses to fimbriae and serogroup C polysaccharide in mice, and IgG:IgM ratios indicated that the responses were thymus-dependent. High bactericidal antibody titres against a serogroup C strain of N. meningitidis were also observed. In a mouse infection model, the conjugate vaccine protected against lethal infection with N. meningitidis. Therefore, B. pertussis fimbriae are effective carrier proteins for meningococcal serogroup C polysaccharide and could produce a vaccine to protect against meningococcal disease and to augment protection against pertussis.
authors.affiliation: Centre for Applied Microbiology and Research, Salisbury SP4 0JG, Wiltshire, UK. karen.reddin@camr.org.uk
authors.forename: K M
authors.initials: KM
authors.lastname: Reddin
authors.forename: A
authors.initials: A
authors.lastname: Crowley-Luke
authors.forename: S O
authors.initials: SO
authors.lastname: Clark
authors.forename: P J
authors.initials: PJ
authors.lastname: Vincent
authors.forename: A R
authors.initials: AR
authors.lastname: Gorringe
authors.forename: M J
authors.initials: MJ
authors.lastname: Hudson
authors.forename: A
authors.initials: A
authors.lastname: Robinson
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001886:Bordetella pertussis / Q000502:physiology*; D002352:Carrier Proteins / Q000008:administration & dosage / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D008168:Lung / Q000382:microbiology; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009345:Neisseria meningitidis / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D014132:Trachea / Q000382:microbiology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000907:Antibodies, Bacterial; D002352:Carrier Proteins; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate