Adjuvanticity of native and detoxified adenylate cyclase toxin of Bordetella pertussis towards co-administered antigens.
The cell-invasive adenylate cyclase toxin (CyaA) of Bordetella pertussis was shown to be highly antigenic in mice, stimulating serum anti-CyaA IgG antibody responses which were able to neutralise the cytotoxic effect of CyaA on J774.2 macrophage-like cells. The effect of co-administration to mice of the fully functional CyaA toxin or a toxin lacking adenylate cyclase enzymic activity (CyaA*) with other antigens from B. pertussis, namely pertussis toxin (PT) or pertussis toxoid (PTd), filamentous haemagglutinin (FHA) and pertactin (PRN), was investigated. CyaA* enhanced the serum IgG antibody responses to each of these antigens whereas, with CyaA, only anti-PRN antibody titres showed a modest increase. Peritoneal macrophages and spleen cells, collected at 2 weeks post-immunisation, were cultured and tested for nitric oxide (NO) and IFNgamma production, respectively, after stimulation in vitro with heat-killed B. pertussis cells or CyaA proteins. NO and IFNgamma production were higher in cells collected from mice immunised with CyaA or CyaA* in combination with a PT, FHA and PRN antigen mixture than from those taken from mice injected with antigen mixture alone, again with CyaA* acting as a better adjuvant than CyaA. The apparent enhancement of immune responses to the antigen mixture by CyaA* in particular was not paralleled by increased protection of mice against aerosol challenge with B. pertussis, but a statistically significant increase in protection was seen after intranasal challenge with B. parapertussis.
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK.
Julia
J
Macdonald-Fyall
Dorothy
D
Xing
Michael
M
Corbel
Susan
S
Baillie
Roger
R
Parton
John
J
Coote
D000262:Adenylyl Cyclases / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D015153:Blotting, Western; D001886:Bordetella pertussis / Q000201:enzymology* / Q000276:immunology*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D006388:Hemagglutinins / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D037342:Pertussis Toxin / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D022282:Vaccines, Acellular / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000276:immunology; D014917:Whooping Cough / Q000276:immunology / Q000517:prevention & control
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D006388:Hemagglutinins; D022282:Vaccines, Acellular; D010566:Virulence Factors, Bordetella; D009569:Nitric Oxide; C068929:pertactin; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases