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.
Macdonald-Fyall
Julia
J
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK.
Xing
Dorothy
D
Corbel
Michael
M
Baillie
Susan
S
Parton
Roger
R
Coote
John
J
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