Adjuvant activity of free Bordetella pertussis filamentous haemagglutinin delivered by mucosal routes.
The development of safe and potent mucosal adjuvants remains a major objective in vaccinology. The potential usefulness of filamentous haemagglutinin (FHA) of Bordetella pertussis as an adjuvant was assessed in a mouse model. The glutathione-S-transferase of Schistosoma mansoni (Sm28GST) was used for intranasal administration, while the gut-resistant keyhole limpet haemocyanin (KLH) was administrated by the oral route. For both antigens, coadministration with FHA increased antigen-specific immunoglobulin titres. This adjuvant effect did not require chemical cross-linking or direct interaction between FHA and the antigen tested. FHA also behaved as an adjuvant by the subcutaneous route, indicating that its adjuvanticity is not restricted to binding to mucosal surfaces. The FHA-induced adjuvanticity was also observed in mice with high anti-FHA antibody titres as a result of antipertussis vaccination, indicating that pre-existing anti-FHA antibodies do not impair FHA adjuvanticity. No mRNA coding for proinflammatory cytokines was induced in the lungs after intranasal FHA administration. However, an increase in the levels of mRNAs coding for B7-1, transforming growth factor (TGF)-beta and major histocompatibility complex (MHC)-II was detected in the lungs after FHA administration. Although the molecular mechanisms of the FHA-induced adjuvanticity remain to be elucidated, the data presented here indicate that this adhesin, already assessed for human use as a pertussis vaccine constituent, represents a promising adjuvant to improve the humoral immune response when given by mucosal routes.
Poulain-Godefroy
O
O
INSERM U547, Institut Pasteur de Lille, Lille Cedex, France. odile.poulain@pasteur-lille.fr
Menozzi
F D
FD
Alonso
S
S
Vendeville
C
C
Capron
A
A
Locht
C
C
Riveau
G
G
D018829:Adhesins, Bacterial / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics; D005260:Female; D005802:Genes, MHC Class II; D005982:Glutathione Transferase / Q000276:immunology; D006388:Hemagglutinins / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D006433:Hemocyanins / Q000276:immunology; D051379:Mice; D012550:Schistosoma mansoni / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D006388:Hemagglutinins; D016212:Transforming Growth Factor beta; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis; D006433:Hemocyanins; D005982:Glutathione Transferase; C032808:keyhole-limpet hemocyanin