title: Protection of mice from rabies by intranasal immunization with inactivated rabies virus.
abstract: The mucosal immunization method is a needle-free alternative way of vaccination. This study evaluated the efficacy of mucosal immunization for rabies. Mice were intranasally administered five times with inactivated and concentrated rabies virus antigen (CRV) supplemented with or without cholera toxin (CT). The anti-rabies virus antibody titer of mice intranasally immunized with CRV plus CT (CRV/CT) was comparable to that of mice intraperitoneally immunized twice with the same amount of CRV. Virus neutralizing (VNA) titers of mice immunized intranasally with CRV/CT were slightly lower than those of intraperitoneally immunized mice. Both anti-rabies virus ELISA antibody and VNA titers of mice immunized with CRV without CT were significantly lower than those of mice immunized with CRV/CT. In mice intranasally immunized with CRV/CT, and intraperitoneally immunized mice, high levels of IgG(2a) antibody were detected, suggesting the activation of Th1-driven cellular immunity by the two ways of immunization. All immunized mice were challenged intracerebrally with a lethal dose of virulent rabies virus CVS strain. The survival rates of mice immunized with CRV/CT and CRV without CT were 67% and 17%, respectively, while the rate of intraperitoneally immunized mice was 100%. Antigen-specific whole IgG and IgG(2a), and VNA titers of survived mice were significantly higher than those of dead mice at the challenge day. These data suggest the possibility of intranasal immunization with inactivated antigen as a rabies vaccination strategy and the importance of a mucosal adjuvant such as CT.
authors.affiliation: Department of Global Animal Resource Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoneda
authors.forename: Kotaro
authors.initials: K
authors.lastname: Tuchiya
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takashima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Arakawa
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Tsuji
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Matsumoto
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002772:Cholera Toxin / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization / Q000379:methods*; D007074:Immunoglobulin G / Q000097:blood; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa; D011818:Rabies / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000008:administration & dosage*; D012376:Rodent Diseases / Q000517:prevention & control*; D015164:Vaccines, Inactivated / Q000008:administration & dosage
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D011819:Rabies Vaccines; D015164:Vaccines, Inactivated; D002772:Cholera Toxin