HIV mucosal vaccine: Nasal immunization with rBCG-V3J1 induces a long termV3J1 peptide-specific neutralizing immunity in Th1- and Th2-deficient conditions

In the vaccine strategy against HIV, bacillus Calmette-Guerin (BCG), a live attenuated strain of Mycobacterium bovis, is considered to be one of poten tial vectors for mucosal delivery of vaccine Ag. We analyzed the induction of the Ag-specific Ab response by nasal immunization with recombinant BCG v ector-based vaccine (rBCG-V3J1) that can secrete the V3 principal neutraliz ing epitope of HIV. Alice were nasally immunized with rBCG-V3J1 (10 mug) th ree times at weekly intervals. Four weeks after the initial immunization, h igh titers of V3J1-specific IgG Abs were seen in serum. These high levels o f HIV-specific serum IgG responses were maintained for > 12 mo following na sal immunization without any booster immunization. V3J1-specific IgG-produc ing cells were detected in mononuclear cells isolated from spleen, nasal ca vity, and salivary gland of the nasally vaccinated mice. Nasal rBCG-V3J1 al so induced high levels of prolonged HIV-specific serum IgG responses in Th1 (IFN-gamma (-/-))- or Th2 (IL-4(-/-))-immunodeficient mice. Further, IgG3 was highest among V3 peptide-specific IgG subclass Ab responses in these im munodeficient mice as well as in wild-type mice. In addition, this Ag-speci fic serum IgG Abs induced by nasal immunization with rBCG-V3J1 possessed th e ability to neutralize clinical isolate of HIV in vitro. These results sug gested that the nasal rBCG-V3J1 system might be used as a therapeutic vacci ne in addition to a prophylaxis vaccine for the control of AIDS.