Background:  Several recent studies have shown that pathogenic HIV/SIV infections are associated with a rapid, dramatic, virus-induced depletion of memory CD4⁺ T cells from mucosal-associated lymphoid tissues (MALT). These studies led to a model in which the MALT CD4⁺ T-cell depletion plays a key role in the pathogenesis of AIDS. As such, a desirable property of a candidate AIDS vaccine would be to generate high numbers of HIV-specific memory CD8₊ T cells in the mucosa that may limit this early loss of CD4⁺ T cells. The aim of this study was to assess the level of SIV-specific CD8⁺ T cells in mucosal tissues of rhesus macaques immunized with 2 modified vaccinia virus Ankara (MVA)-vectored candidate AIDS vaccines.

Methods:  Of 5 groups of MaMu-A01 rhesus macaques, 2 were inoculated either intramuscularly or intradermally with 2x10⁸ PFU of wild type MVA or an MVA vector with the uracyl DNA glycosylase (UDG) gene deleted (MVA∆UDG). Both vectors expressed SIV_mac239 gag and tat. All animals received 3 immunizations 6 weeks apart. Tissues examined included peripheral blood, lymph nodes, rectal mucosa (via rectal biopsies) and lung (via broncho-alveolar lavage). Lymphocytes isolated from these tissues were examined by flow cytometry and gag- and tat-specific CD8⁺ T cells were assessed by tetramer staining.

Results:  In all animals studied, both wild type MVA and MVAΔUDG induced detectable levels of gag-specific CD8⁺ T cells, with levels of 0.25 to 2.2% in peripheral blood; 0.03 to 0.55% in lymh node; 0.03 to 1.09% in lung; and 0.33 to 16.2% in rectal mucosa at day 7 after the third immunization. Tat-specific CD8⁺ T cells were also detectable in all tissues of all animals, albeit at lower levels. Interestingly, the highest levels of SIV-specific CD8⁺ T cells were found in the rectal mucosa, with the majority of these cells displaying a phenotype (CD28^–CD95⁺) indicative of full differentiation to effector or effector-memory T cells.

Conclusions:  Repeated immunization with MVA vectors that express SIV-gene products results in levels of SIV-specific effector CD8⁺ T cells in gut-associated lymphoid tissues that are higher than those observed in peripheral blood, lymph node, and lung. Challenge studies are in progress to determine whether and to what extent these intestinal mucosal SIV-specific CD8⁺ T cells protect from the early depletion of MALT CD4⁺ T cells described in unvaccinated SIV-infected rhesus macaques.