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Vaccine. 2004 Oct 22;22(31-32):4270-81.

Adjuvanticity of native and detoxified adenylate cyclase toxin of Bordetella pertussis towards co-administered antigens.

Author information

1
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK.

Abstract

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.

PMID:
15474718
DOI:
10.1016/j.vaccine.2004.04.033
[Indexed for MEDLINE]

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