title: Mucosal or targeted lymph node immunization of macaques with a particulate SIVp27 protein elicits virus-specific CTL in the genito-rectal mucosa and draining lymph nodes.
abstract: The major routes of HIV transmission are through the rectal and cervico-vaginal mucosa. To prevent dissemination of HIV to the regional lymph nodes (LNs), an effective vaccine may need to stimulate CTL in the rectal or genital tract and the draining LNs. We report that mucosal immunization by the recto-oral and vagino-oral route or s.c. immunization targeting the iliac LNs with a particulate SIVp27:Ty-VLP vaccine elicits SIVgag-specific CTL in the regional LNs as well as in the spleen and PBMC. Targeted LN immunization with this vaccine elicited MHC class I-restricted CD8+ CTL responses, and the highest frequency of CTL was found in the iliac LNs. Moreover, SIVgag-specific CTL activity was detected in short term T cell lines established in mononuclear cells eluted from the rectal and cervico-vaginal mucosa. The relative frequency of CTL in short term cell lines prepared from the rectal mucosa (21/113 or 18.6%) was similar to that obtained from the cervico-vaginal mucosa (16/79 or 20.3%). Examination of the relative frequency of CTL to the T cell epitopes residing within SIVp27 showed a higher frequency in iliac LN cells to peptide aa 41-70 than in that to peptide aa 121-150, and this was significant after both recto-oral (chi-squared 6.500, p < 0.02) and vagino-oral (chi-squared = 10.391, p < 0.01) immunization. In contrast, the relative frequency of CTL in PBMC to peptide aa 41-70 (15.5%) was comparable to that elicited by peptide aa 121-150 (17.6%). This study provides novel evidence that mucosal or targeted LN immunization can generate anti-SIV CTL in the rectal and genital mucosa, in the draining LNs, and in the central lymphoid system.
authors.affiliation: Department of Immunology, United Medical and Dental Schools of Guy's and St. Thomas' Hospital, London, United Kingdom.
authors.forename: L S
authors.initials: LS
authors.lastname: Klavinskis
authors.forename: L A
authors.initials: LA
authors.lastname: Bergmeier
authors.forename: L
authors.initials: L
authors.lastname: Gao
authors.forename: E
authors.initials: E
authors.lastname: Mitchell
authors.forename: R G
authors.initials: RG
authors.lastname: Ward
authors.forename: G
authors.initials: G
authors.lastname: Layton
authors.forename: R
authors.initials: R
authors.lastname: Brookes
authors.forename: N J
authors.initials: NJ
authors.lastname: Meyers
authors.forename: T
authors.initials: T
authors.lastname: Lehner
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002584:Cervix Uteri / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D015683:Gene Products, gag / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D018928:Immunity, Mucosal; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D008253:Macaca mulatta; D012007:Rectum / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014621:Vagina / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I; D014765:Viral Vaccines