title: Mucosal and systemic immunogenicity of a recombinant, non-ADP-ribosylating pertussis toxin: effects of formaldehyde treatment.
abstract: The effect of formaldehyde treatment on the mucosal and systemic immunogenicity of the genetically detoxified pertussis toxin (PT-9K/129G) was investigated. Groups of BALB/c were immunized intranasally (i.n.) or subcutaneously (s.c.) with untreated, lightly formaldehyde treated (LFT) or heavily formaldehyde treated (HFT) recombinant pertussis toxin (PT) mutant, PT-9K/129G. Intranasal immunization with native PT-9K/ 129G induced significant levels of anti-toxin antibodies in serum and IgA anti-toxin responses in nasal and lung lavages of these mice. Similar local and systemic responses were observed following intransal immunization with LFT toxin. However, i.n. immunization with HFT toxin failed to induce a local IgA response and elicited a much diminished anti-toxin response in the serum. In contrast, the total antibody response following s.c. immunization was not significantly affected. In addition, i.n. immunization with native PT-9K/129G induced low but detectable levels of toxin neutralizing antibodies in the serum. These results show that native PT-9K/129G protein acts as a mucosal immunogen in mice and that this activity is greatly diminished by HFT of the protein.
authors.affiliation: Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Cropley
authors.forename: G
authors.initials: G
authors.lastname: Douce
authors.forename: M
authors.initials: M
authors.lastname: Roberts
authors.forename: S
authors.initials: S
authors.lastname: Chatfield
authors.forename: M
authors.initials: M
authors.lastname: Pizza
authors.forename: I
authors.initials: I
authors.lastname: Marsili
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
authors.forename: G
authors.initials: G
authors.lastname: Dougan
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D001886:Bordetella pertussis / Q000276:immunology; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology*; D018928:Immunity, Mucosal / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology / Q000382:microbiology; D009500:Neutralization Tests; D037342:Pertussis Toxin; D010567:Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology*; D011065:Poly(ADP-ribose) Polymerases / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D010567:Pertussis Vaccine; D015164:Vaccines, Inactivated; D014614:Vaccines, Synthetic; D010566:Virulence Factors, Bordetella; D005557:Formaldehyde; D011065:Poly(ADP-ribose) Polymerases; D037342:Pertussis Toxin