title: Naked DNA when co-administered intranasally with heat-labile enterotoxin of Escherichia coli primes effectively for systemic B- and T-cell responses to the encoded antigen.
abstract: In this study a novel prime-boost immunisation strategy was evaluated. Priming of BALB/c mice by the intranasal route with plasmid DNA encoding beta-galactosidase (LacZ) with or without heat-labile enterotoxin (LT) of Escherichia coli as a mucosal adjuvant, resulted in the induction of weak serum antibody and proliferative T-cell responses. However, following an intraperitoneal booster injection with the beta-galactosidase protein (beta-gal), strong antibody and proliferative T-cell responses were induced in all the mice. These responses were highest in mice primed intranasally with a mixture of LacZ+LT as compared to those mice primed with DNA (LacZ) or protein (beta-gal) alone. Moreover, LacZ+LT primed mice produced high avidity antibodies and the subclasses of serum antibodies were IgG1 and IgG2a, suggesting a mixed Th1/Th2-type response. Priming of mice with either protein (beta-gal) or DNA (LacZ) alone, produced predominantly IgG1 antibodies, suggesting a Th2-type response. These findings suggest that the use of a heterologous DNA-prime, protein-boost immunisation scheme combining different routes of administration, might be an advantageous strategy for the induction of accelerated immune responses.
authors.affiliation: Department of Pathology and Infectious Diseases, The Royal Veterinary College, Royal College Street, NW I OTU, London, UK. tkanello@rvc.ac.uk
authors.forename: T S
authors.initials: TS
authors.lastname: Kanellos
authors.forename: D K
authors.initials: DK
authors.lastname: Byarugaba
authors.forename: P H
authors.initials: PH
authors.lastname: Russell
authors.forename: C R
authors.initials: CR
authors.lastname: Howard
authors.forename: C D
authors.initials: CD
authors.lastname: Partidos
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000276:immunology; D000915:Antibody Affinity; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000494:pharmacology; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology; D004269:DNA, Bacterial / Q000008:administration & dosage* / Q000235:genetics; D004768:Enterotoxins / Q000008:administration & dosage* / Q000494:pharmacology; D029968:Escherichia coli Proteins; D005260:Female; D007111:Immunity, Cellular; D007114:Immunization / Q000379:methods*; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007274:Injections, Intraperitoneal; D007763:Lac Operon; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004269:DNA, Bacterial; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D019444:Vaccines, DNA; C027538:heat-labile enterotoxin, E coli; D001616:beta-Galactosidase