title: Immunization with adenovirus at the large intestinal mucosa as an effective vaccination strategy against sexually transmitted viral infection.
abstract: The large intestinal mucosa contains immunological structures that may potentially serve as a site for induction of mucosal immunity against infections. Adenovirus (Ad), which is effective in gene transfer to epithelia, may be an ideal antigen delivery system for vaccination at the large intestinal mucosa. To investigate this potential, we immunized mice with recombinant replication-deficient Ad through a single intracolorectal (ICR) administration. Effective transfer of encoded genes was found in both the epithelial layer and lamina propria of the colorectal mucosa. Dendritic cells were able to transfer antigen to the draining lymph nodes, where antigen-specific CD8(+) T cells were primed. Functional antigen-specific CD8(+) T cells and IgA-specific antibodies were detected during the effector phase in the large intestine. Compared to other immunization routes (intranasal, subcutaneous), ICR immunization induced stronger colorectal immune responses and more potent protection against rectal challenge with pathogenic viruses. Further, this immunization strategy provided vaginal protection, more potent than that induced by vaccination in the nose or skin. Therefore, large intestine mucosal immunization using Ad represents an effective vaccination strategy against virus infection at both rectal and vaginal mucosal tissue sites.
authors.affiliation: Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada. zhuq@mail.nih.gov
authors.forename: Q
authors.initials: Q
authors.lastname: Zhu
authors.forename: C W
authors.initials: CW
authors.lastname: Thomson
authors.forename: K L
authors.initials: KL
authors.lastname: Rosenthal
authors.forename: M R
authors.initials: MR
authors.lastname: McDermott
authors.forename: S M
authors.initials: SM
authors.lastname: Collins
authors.forename: J
authors.initials: J
authors.lastname: Gauldie
mesh_terms: D000256:Adenoviridae; D000818:Animals; D002522:Chlorocebus aethiops; D005260:Female; D018014:Gene Transfer Techniques; D018928:Immunity, Mucosal / Q000235:genetics; D007114:Immunization / Q000379:methods*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000821:virology; D007420:Intestine, Large / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015229:Sexually Transmitted Diseases, Viral / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D014709:Vero Cells