ORAL IMMUNIZATION WITH RECOMBINANT MYCOBACTERIUM-BOVIS BCG SIMIAN IMMUNODEFICIENCY VIRUS NEF INDUCES LOCAL AND SYSTEMIC CYTOTOXIC T-LYMPHOCYTE RESPONSES IN MICE

Recombinant live Mycobacterium bovis BCG vectors (rBCG) induce strong cellular and humoral immune responses against various antigens after e ither systemic or oral immunization of mice. Cytotoxic T-lymphocyte (C TL) responses may contribute to the control of human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) infections whose po rtal of entry is the gastrointestinal or genital mucosa. In this study , we immunized BALB/c mice with a recombinant BCG SIV nef and observed its behavior in oropharyngeal and target organ lymphoid tissues. The cellular immune responses, particularly the intestinal. intraepithelia l and systemic CTL responses, were investigated. The results showed th at rBCG SIV nef translocated the oropharyngeal mucosa and intestinal e pithelium. It diffused to and persisted in target lymphoid organs. Spe cific SIV Nef peptide proliferative responses and cytokine production were observed. Strong systemic and mucosal CTL responses were induced. In particular, we demonstrated direct specific anti-Nef CTL in intest inal intraepithelial CD8 beta(+) T cells. These findings provide evide nce that orally administered rBCG SIV nef may contribute to local defe nses against viral invasion. Therefore, rBCG SIV nef could be a candid ate vaccine to protect against SIV infection and may be used to develo p an oral rBCG HIV nef vaccine.