title: Effectiveness of cholera toxin B subunit as an adjuvant for nasal influenza vaccination despite pre-existing immunity to CTB.
abstract: In a previous paper, it was shown that cholera toxin B subunit (CTB) augments the production of protective antibodies to influenza virus when CTB is inoculated intranasally into Balb/c mice together with influenza HA vaccine. The present study was designed to determine whether the effectiveness of CTB as a potent adjuvant for nasal vaccination could be limited by pre-existing immunity to CTB. Mice were sensitized by intranasal inoculation of either 1 or 0.05 microgram of CTB 2, 4 and/or 6 weeks before nasal vaccination. They were then vaccinated by either a single inoculation of vaccine together with 1 microgram of CTB or a two-dose regimen, composed of a primary inoculation of vaccine together with 0.05 microgram of CTB and a subsequent inoculation of vaccine alone. Levels of nasal IgA antibodies to CTB increased with the increase of the dose of CTB and the frequency of CTB-inoculation. Pre-existing immunity to CTB, however, did not significantly reduce the levels of both nasal IgA and serum haemagglutination-inhibiting (HI) antibodies to influenza virus and did not change the ability of the vaccinated mice to resist viral challenge. These results suggest that a relatively low dose of CTB could be inoculated repeatedly into animals as an adjuvant for nasal vaccination.
authors.affiliation: Department of Pathology, National Institute of Health, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tamura
authors.forename: H
authors.initials: H
authors.lastname: Funato
authors.forename: T
authors.initials: T
authors.lastname: Nagamine
authors.forename: C
authors.initials: C
authors.lastname: Aizawa
authors.forename: T
authors.initials: T
authors.lastname: Kurata
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D002772:Cholera Toxin / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D007070:Immunoglobulin A / Q000032:analysis; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007252:Influenza Vaccines; D010446:Peptide Fragments; D002772:Cholera Toxin