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

The major routes of HIV transmission are through the rectal and cervic o-vaginal mucosa, To prevent dissemination of HIV to the regional lymp h nodes (LNs), an effective vaccine may need to stimulate CTL in the r ectal or genital tract and the draining LNs, We report that mucosal im munization by the recto-oral and vagino-oral route or s.c. immunizatio n targeting the iliac LNs with a particulate SIVp27:Ty-VLP vaccine eli cits SIVgag-specific CTL in the regional LNs as well as in the spleen and PBMC, Targeted LN immunization with this vaccine elicited MHC clas s 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 freque ncy of CTL in short term cell lines prepared from the rectal mucosa (2 1/113 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 frequenc y 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(2) = 6.500, p < 0.02) and vagino-oral (chi(2) = 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 immuniz ation can generate anti-SIV CTL in the rectal and genital mucosa, in t he draining LNs, and in the central lymphoid system.