title: Parenteral and mucosal prime-boost immunization strategies in mice with hepatitis B surface antigen and CpG DNA.
abstract: Synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG ODN) are potent adjuvants to protein antigens administered by parenteral or mucosal routes to BALB/c mice. To date, there have been no studies using combined parenteral/mucosal approaches with CpG DNA as adjuvant. In this study we evaluated different parenteral prime-mucosal boost and mucosal prime-parenteral boost strategies using hepatitis B surface antigen (HBsAg) alone or with different adjuvants: aluminum hydroxide (alum), cholera toxin (CT), CpG ODN. In addition, since CpG ODN has previously been shown to act synergistically with other adjuvants after parenteral or mucosal delivery, we also evaluated adjuvant combinations: alum+CpG ODN and CT+CpG ODN. The effects of adjuvant and administration strategy on systemic and mucosal humoral responses were measured, as well as cell-mediated immune responses (cytotoxic T lymphocyte activity). These results were compared to parenteral only or mucosal only strategies. Our findings demonstrate that parenteral immunization can prime for mucosal responses even when different lymph nodes were being targeted. HBsAg-specific immune responses (IgG in plasma, cytotoxic T lymphocytes) induced by parenteral prime could all be significantly enhanced by mucosal boosting and despite the fact that intramuscular immunization alone could not induce mucosal IgA, it could prime for a subsequent mucosal boost. In addition, the presence of adjuvant at time of boosting could influence the nature of subsequent immune responses (Th1 vs. Th2). Mice primed intranasally could have their systemic immune responses boosted with a parenteral administration and it was also possible to enhance mucosal responses induced by intranasal prime with an intramuscular boost.
authors.affiliation: Coley Pharmaceutical Group, 725 Parkdale Avenue, K1Y 4E9, Ottawa, ON, Canada. mmccluskie@coleypharma.com
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McCluskie
authors.forename: Risini D
authors.initials: RD
authors.lastname: Weeratna
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Payette
authors.forename: Heather L
authors.initials: HL
authors.lastname: Davis
mesh_terms: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000818:Animals; D002772:Cholera Toxin / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; C408982:CPG-oligonucleotide; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D009838:Oligodeoxyribonucleotides; D014614:Vaccines, Synthetic; C041524:aluminum sulfate; D002772:Cholera Toxin