HIV mucosal vaccine: nasal immunization with rBCG-V3J1 induces a long-term V3J1 peptide-specific neutralizing immunity in Th1- and Th2-deficient condition

Abstract

In the vaccine strategy against HIV, the bacillus Calmette–Guerin (BCG), a live attenuated strain of Mycobacterium bovis, is considered to be one of the potential vectors for mucosal delivery of antigens. We analyzed the induction of antigen-specific antibodies by nasal immunization with recombinant BCG vector-based vaccine (rBCG-V3J1) that secretes the V3 principal neutralizing epitope of HIV [Proc. Natl. Acad. Sci. U. S. A. 92 (1063) 1995]. C57BL/6 mice were nasally immunized with the rBCG-V3J1 (10 μg) four times by weekly intervals. After 1 week of the final immunization, V3J1-specific IgG was seen in the serum. However, antigen-specific secretary and serum IgA antibodies were not induced. High levels of antigen-specific serum IgG responses were maintained for 6 months following the nasal immunization. Antigen-specific IgG-producing cells were detected in mononuclear cells isolated from spleen, nasal cavity, and salivary gland of the nasally vaccinized mice. Furthermore, antigen-specific IgG antibodies induced by nasal immunization with rBCG-V3J1 possessed the ability to neutralize HIV in vitro . Collectively, nasal immunization together with rBCG-V3J1 is considered to be a powerful vaccination regimen for the induction of effective V3J1-specific immune responses. We are currently investigating antigen-specific CTL activity and cytokine production following nasal vaccination with rBCG-V3J1.