title: Intranasal immunization of mice with recombinant Streptococcus gordonii expressing NadA of Neisseria meningitidis induces systemic bactericidal antibodies and local IgA.
abstract: NadA and NhhA, two surface proteins of serogroup B Neisseria meningitidis identified as candidate vaccine antigens, were expressed on the surface of the human oral commensal bacterium Streptococcus gordonii. Recombinant strains were used to immunize BALB/c mice by the intranasal route and the local and systemic immune response was assessed. Mice were inoculated with recombinant bacteria administered alone or with LTR72, a partially inactivated mutant of Escherichia coli heat-labile enterotoxin, as a mucosal adjuvant. Intranasal immunization with live bacteria expressing NadA induced a significant serum antibody response, with a prevalence of the IgG2a subclass, bactericidal activity in the sera of 71% of animals, and a NadA-specific IgA response in nasal and bronchoalveolar lavages. A formalin-inactivated recombinant strain of S. gordonii expressing NadA was also administered intranasally, inducing a systemic and mucosal humoral response comparable to that of live bacteria. The administration of recombinant bacteria with the mucosal adjuvant LTR72 stimulated a stronger systemic antibody response, protective in 85% of sera, while did not increase the local IgA response. Recombinant S. gordonii expressing NhhA induced a systemic but not mucosal antibody response. These data support the role of NadA as vaccine candidate against serogroup B meningococci, and the use of S. gordonii as vector for intranasal vaccination.
authors.affiliation: Laboratorio di Microbiologia Molecolare e Biotecnologia (LA.M.M.B.), Dipartimento di Biologia Molecolare, Università di Siena, Policlinico Le Scotte, V Lotto Piano 1, 53100 Siena, Italy. ciabattini@unisi.it
authors.forename: Annalisa
authors.initials: A
authors.lastname: Ciabattini
authors.forename: Barbara
authors.initials: B
authors.lastname: Giomarelli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Parigi
authors.forename: Damiana
authors.initials: D
authors.lastname: Chiavolini
authors.forename: Elena
authors.initials: E
authors.lastname: Pettini
authors.forename: Beatrice
authors.initials: B
authors.lastname: Aricò
authors.forename: Marzia M
authors.initials: MM
authors.lastname: Giuliani
authors.forename: Laura
authors.initials: L
authors.lastname: Santini
authors.forename: Donata
authors.initials: D
authors.lastname: Medaglini
authors.forename: Gianni
authors.initials: G
authors.lastname: Pozzi
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004768:Enterotoxins / Q000008:administration & dosage / Q000494:pharmacology; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007070:Immunoglobulin A / Q000032:analysis*; D007074:Immunoglobulin G / Q000097:blood; D008585:Meningitis, Meningococcal / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D009297:Nasal Mucosa / Q000276:immunology; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology; D054773:Streptococcus gordonii / Q000235:genetics / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; C501982:NadA protein, Neisseria meningitidis; D015164:Vaccines, Inactivated; D014614:Vaccines, Synthetic; C027538:heat-labile enterotoxin, E coli