title: Enhancing activity of mycobacterial cell-derived adjuvants on immunogenicity of recombinant human hepatitis B virus vaccine.
abstract: In a previous study, we demonstrated that a lipophilic derivative of muramyl dipeptide [MDP-Lys(L18)] augmented antibody response to recombinant human hepatitis B surface antigen (rhHBsAg) when it was co-immunized with rhHBsAg solubilized in PBS. Here, we examined adjuvant activity of two bacterial cell-derived adjuvants such as Bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) and trehalose-6,6'-dimycolate (TDM), to enhance immunogenicity of rhHBsAg, comparing their activity with that of MDP-Lys(L18). In an animal model where mice were immunized subcutaneously (s.c.) with rhHBsAg (25 micrograms/mouse) admixed with 100 micrograms/mouse of BCG-CWS (Vac/BCG-CWS) or 50 micrograms/mouse of TDM (Vac/TDM) in o/w emulsion formulation, both mice immunized with Vac/BCG-CWS and Vac/TDM showed higher antibody titres to HB antigen than those of mice immunized with the recombinant vaccine alone. The activity of BCG-CWS and TDM to enhance antibody induction seemed to be almost the same with that of MDP-Lys(L18). Furthermore, the enhanced antibody response raised by these adjuvants was shown to be due to high titres of HB antigen-specific IgG1. In addition, the activity of these three adjuvants to enhance antibody response was shown to be higher than that of the present clinical vaccine, aluminium hydroxide-attached rhHBsAg (rhHBsAg-alum). In an analysis of delayed-type hypersensitivity (DTH) reaction where mice were immunized with rhHBsAg admixed with or without each adjuvant in o/w emulsion and followed by intrafootpad (i.f.) injection of rhHBsAg 4 weeks after immunization, mice immunized with Vac/BCG-CWS and Vac/TDM as well as Vac/MDP-Lys(L18) showed a significant increment of swelling reaction. These results suggest that BCG-CWS, TDM and MDP-Lys(L18) are potential adjuvants to enhance the immunogenicity of rhHBsAg to induce humoral and cellular responses.
authors.affiliation: Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Koike
authors.forename: Y C
authors.initials: YC
authors.lastname: Yoo
authors.forename: M
authors.initials: M
authors.lastname: Mitobe
authors.forename: T
authors.initials: T
authors.lastname: Oka
authors.forename: K
authors.initials: K
authors.lastname: Okuma
authors.forename: S
authors.initials: S
authors.lastname: Tono-oka
authors.forename: I
authors.initials: I
authors.lastname: Azuma
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D002473:Cell Wall / Q000276:immunology; D003311:Cord Factors / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000096:biosynthesis*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D003311:Cord Factors; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007132:Immunoglobulin Isotypes; D011994:Recombinant Proteins; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C036866:romurtide