title: Intradermal delivery of recombinant vaccinia virus vector DIs induces gut-mucosal immunity.
abstract: Antigen-specific mucosal immunity is generally induced by the stimulation of inductive mucosal sites. In this study, we found that the replication-deficient vaccinia virus vector, DIs, generates antigen-specific mucosal immunity and systemic responses. Following intradermal injection of recombinant DIs expressing simian immunodeficiency virus gag (rDIsSIVgag), we observed increased levels of SIV p27-specific IgA and IgG antibodies in faecal extracts and plasma samples, and antibody-forming cells in the intestinal mucosa and spleen of C57BL/6 mice. Antibodies against p27 were not detected in nasal washes, saliva, and vaginal washes. The enhanced mucosal and systemic immunity persisted for 1 year of observation. Induction of Gag-specific IFN-gamma spot-forming CD8(+) T cells in the spleen, small intestinal intraepithelial lymphocytes, and submandibular lymph nodes was observed in the intradermally injected mice. Heat-inactivated rDIsSIVgag rarely induced antigen-specific humoral and T-helper immunity. Moreover, rDIsSIVgag was detected in MHC class II IA antigen-positive (IA(+)) cells at the injection site. Consequently, intradermal delivery of rDIs effectively induces antigen-specific humoral and cellular immunity in gut-mucosal tissues of mice. Our data suggest that intradermal injection of an rDIs vaccine may be useful against mucosally transmitted pathogens.
authors.affiliation: Department of Microbiology, School of Medicine, Iwate Medical University, Morioka, Iwate, Japan. nyoshino@iwate-med.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Yoshino
authors.forename: M
authors.initials: M
authors.lastname: Kanekiyo
authors.forename: Y
authors.initials: Y
authors.lastname: Hagiwara
authors.forename: T
authors.initials: T
authors.lastname: Okamura
authors.forename: K
authors.initials: K
authors.lastname: Someya
authors.forename: K
authors.initials: K
authors.lastname: Matsuo
authors.forename: Y
authors.initials: Y
authors.lastname: Ami
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Honda
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D018709:Statistics, Nonparametric; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D015683:Gene Products, gag; D018449:SAIDS Vaccines; D007371:Interferon-gamma; D004247:DNA