title: Mucosal immunization against hepatitis B virus by intranasal co-administration of recombinant hepatitis B surface antigen and recombinant cholera toxin B subunit as an adjuvant.
abstract: Recombinant cholera toxin B subunit (rCTB) produced by Bacillus brevis carrying pNU212-CTB has been previously found to be a potent mucosal adjuvant to aluminium-non-adsorbed tetanus toxoid (nTT) and diphtheria toxoid (nDT) co-administered intranasally, and the possibility of needle-free inoculation of these vaccines with rCTB has been suggested. In this paper we examined the potentiality of rCTB as a mucosal adjuvant to aluminium-non-adsorbed yeast-derived recombinant hepatitis B surface antigen (rHBs) being a particulate antigen when administered intranasally with rCTB. In-house ELISA showed that a mixture of rHBs (1 or 5 microg) and rCTB (10 microg) elevated not only systemic responses but also mucosal immune responses at the nasal cavity, the lung, the saliva, the small intestine and the vagina against rHBs, and these could be further increased with higher doses of antigen. With antibody isotypes of IgG, there were equally high levels of serum HBs-specific IgG1, IgG2a and IgG2b antibodies and induction of mixed Th1- and Th2-type responses was considered to occur in combination of rHBs and rCTB. Serum anti-HBs titres in almost all mice obtained from sandwich EIA using a commercial kit were higher than 1000 milli-international units ml(-1) (mIU ml(-1)). These results show that rCTB is also very effective as a mucosal adjuvant for a particulate antigen like rHBs, as well as soluble antigens like nTT and nDT reported previously, suggesting the possibility of intranasal immunization with rHBs plus rCTB in humans.
authors.affiliation: Department of Microbiology, Nagoya City University Medical School, Mizuho-ku, 467-8601, Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Isaka
authors.forename: Y
authors.initials: Y
authors.lastname: Yasuda
authors.forename: M
authors.initials: M
authors.lastname: Mizokami
authors.forename: S
authors.initials: S
authors.lastname: Kozuka
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: K
authors.initials: K
authors.lastname: Matano
authors.forename: J
authors.initials: J
authors.lastname: Maeyama
authors.forename: K
authors.initials: K
authors.lastname: Mizuno
authors.forename: K
authors.initials: K
authors.lastname: Morokuma
authors.forename: K
authors.initials: K
authors.lastname: Ohkuma
authors.forename: N
authors.initials: N
authors.lastname: Goto
authors.forename: K
authors.initials: K
authors.lastname: Tochikubo
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D002772:Cholera Toxin / Q000008:administration & dosage; D005260:Female; D006510:Hepatitis B Antibodies / Q000096:biosynthesis / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage; D017325:Hepatitis B Vaccines / Q000008:administration & dosage*; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D014614:Vaccines, Synthetic / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D002772:Cholera Toxin