title: Enhancement of antibody production against rabies virus by uridine 5'-triphosphate in mice.
abstract: Extracellular nucleotides such as adenosine 5'-triphospate (ATP) and uridine 5'-triphosphate (UTP) interact with P2 purinergic receptors on the surface of phagocytic cells and induce various physiological reactions. In this study, the production of antibody in mice immunized with an inactivated rabies vaccine containing these nucleotides was investigated. Injection of inactivated rabies vaccine with UTP, but not with ATP, induced significantly higher serum antibody production in mice. The enhancement of antibody production by UTP was inhibited by an anti-P2Y4 receptor antibody. In an air pouch experiment, UTP treatment increased the number of monocytes and macrophages infiltrating the pouch and up-regulated the gene expression of IL-4 and IL-13 in the regional lymph nodes. These results suggested that UTP admixed with rabies vaccine activates Th2 cells and induces a humoral immune response. Furthermore, the survival rate of mice immunized with a rabies vaccine admixed with UTP before rabies virus challenge was slightly higher than that of control mice. In conclusion, UTP can act as a vaccine adjuvant to enhance antibody production against the rabies virus in mice.
authors.affiliation: Laboratory of Comparative Pathology, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwaki
authors.affiliation: Laboratory of Comparative Pathology, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Laboratory of Comparative Pathology, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ochiai
authors.affiliation: Laboratory of Comparative Pathology, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Umemura
authors.affiliation: Laboratory of Comparative Pathology, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan. Electronic address: sunden@vetmed.hokudai.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sunden
mesh_terms: D000255:Adenosine Triphosphate; D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D005260:Female; D007378:Interleukins / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D011820:Rabies virus / Q000276:immunology*; D014544:Uridine Triphosphate / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007378:Interleukins; D011819:Rabies Vaccines; D000255:Adenosine Triphosphate; D014544:Uridine Triphosphate
keywords: Antibody; P2Y4 receptor; Rabies; UTP; Vaccine