A cocktail of Mycobacterium bovis BCG recombinants expressing the SIV Nef,Env, and Gag antigens induces antibody and cytotoxic responses in mice vaccinated by different mucosal routes

Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing differen t human immunodeficiency virus (HIV) or simian immunodeficiency (SIV) antig ens could be good candidates for the development of vaccines against AIDS. To develop effective HIV/SIV vaccines, humoral and cellular immune response s directed against multiple antigens may be essential for the control of th e infection. In this study we immunized BALB/c mice via different mucosal r outes (oral, aerogenic, nasal, and rectal) with a mixture of three rBCG str ains expressing, respectively, the entire SIVmac251 Nef protein, and large fragments of the Env and Gag proteins. All routes of immunization studied i nduced immunoglobulin A (IgA) antibodies against mycobacterial PPD, SIV Env , and SIV Gag antigens in feces and bronchial lavages as well as specific i mmunoglobulin G (IgG) in serum. Strong, specific cytotoxic responses of spl enocytes against Nef, Env, and Gag was observed whatever the mucosal route of immunization. Therefore, mucosal vaccination with a cocktail of rBCG str ains induces local, specific IgA, systemic IgG, and systemic CTLs against t he three SIV antigens expressed. Rectal and oral routes seemed the most app ropriate route of vaccination to be used to protect against SIV infection.