title: Escherichia coli heat-labile enterotoxin B subunits supplemented with a trace amount of the holotoxin as an adjuvant for nasal influenza vaccine.
abstract: Escherichia coli heat-labile enterotoxin B subunit (LTB) (2 micrograms), supplemented with a trace amount of the holotoxin (LT) (0.02-20 ng), was examined for the adjuvant effect on antibody (Ab) responses against influenza inactivated haemagglutinin (HA) vaccine in Balb/c mice. Each mouse received a primary intranasal (i.n.) inoculation with the vaccine (1.5 micrograms), prepared from PR8 (H1N1) virus, together with LT-containing LTB and in 4 weeks a second i.n. inoculation of the vaccine alone. The inoculation of the vaccine with the LT-containing LTB induced significantly high primary and secondary anti-HA IgA and IgG Ab responses in the nasal wash and the serum, while the vaccine with LTB or less than 2 ng of LT induced little response. The synergistic adjuvant effect was maximal in the concentration of LTB supplemented with 0.2-2 ng of LT. Under these conditions, the augmented IgA and IgG Ab responses, which are cross-protective to PR8 HA molecules, provided complete cross-protection against PR8 virus challenge in mice immunized with heterologous vaccine within the same subtype. These results suggest that LTB containing a trace amount of LT can be used as a potent adjuvant for nasal vaccination of humans against influenza.
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: Asanuma
authors.forename: T
authors.initials: T
authors.lastname: Tomita
authors.forename: K
authors.initials: K
authors.lastname: Komase
authors.forename: K
authors.initials: K
authors.lastname: Kawahara
authors.forename: H
authors.initials: H
authors.lastname: Danbara
authors.forename: N
authors.initials: N
authors.lastname: Hattori
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Nagamine
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001427:Bacterial Toxins / Q000276:immunology* / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D004768:Enterotoxins / Q000276:immunology* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D005260:Female; D006027:Glycosides / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006697:Holothurin / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000187:drug effects / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012616:Sea Cucumbers; D014315:Triterpenes / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D006027:Glycosides; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D011994:Recombinant Proteins; D014315:Triterpenes; D006697:Holothurin; C001883:stichoposide; C027538:heat-labile enterotoxin, E coli