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*
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan;
Department of Otolaryngology and Head and Neck Surgery, Wakayama Medical University School of Medicine, Wakayama, Japan; and
AIDS Research Center, National Institute of Infectious Disease, Tokyo, Japan
In the vaccine strategy against HIV, bacillus Calmette-Guérin
(BCG), a live attenuated strain of Mycobacterium bovis,
is considered to be one of potential vectors for mucosal delivery of
vaccine Ag. We analyzed the induction of the Ag-specific Ab response by
nasal immunization with recombinant BCG vector-based vaccine
(rBCG-V3J1) that can secrete the V3 principal neutralizing epitope of
HIV. Mice were nasally immunized with rBCG-V3J1 (10 µg) three times
at weekly intervals. Four weeks after the initial immunization, high
titers of V3J1-specific IgG Abs were seen in serum. These high levels
of HIV-specific serum IgG responses were maintained for >12 mo
following nasal immunization without any booster immunization.
V3J1-specific IgG-producing cells were detected in mononuclear cells
isolated from spleen, nasal cavity, and salivary gland of the nasally
vaccinated mice. Nasal rBCG-V3J1 also induced high levels of prolonged
HIV-specific serum IgG responses in Th1 (IFN-
-/-)- or
Th2 (IL-4-/-)-immunodeficient mice. Further, IgG3 was
highest among V3 peptide-specific IgG subclass Ab responses
in these immunodeficient mice as well as in wild-type mice. In
addition, this Ag-specific serum IgG Abs induced by nasal immunization
with rBCG-V3J1 possessed the ability to neutralize clinical isolate of
HIV in vitro. These results suggested that the nasal rBCG-V3J1 system
might be used as a therapeutic vaccine in addition to a prophylaxis
vaccine for the control of AIDS.
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