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 microg) 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-gamma(-/-))- 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.

译文

:在针对HIV的疫苗策略中,卡米特-圭兰杆菌(BCG)是牛分枝杆菌的减毒活株,被认为是粘膜递送疫苗Ag的潜在载体之一。我们通过重组BCG载体为基础的疫苗(rBCG-V3J1)经鼻免疫分析了Ag特异性Ab应答的诱导作用,该疫苗可分泌HIV的V3主要中和表位。每周用rBCG-V3J1(10微克)鼻腔免疫小鼠3次。初次免疫后四周,在血清中观察到高滴度的V3J1特异性IgG Abs。在不进行任何加强免疫的情况下,经鼻免疫后,这些高水平的HIV特异性血清IgG反应保持了> 12 mo。在从经鼻接种的小鼠的脾脏,鼻腔和唾液腺分离的单核细胞中检测到V3J1特异性IgG产生细胞。鼻rBCG-V3J1在Th1(IFN-γ(-/-))-或Th2(IL-4(-/-))免疫缺陷小鼠中也诱导了高水平的长时间HIV特异性血清IgG反应。此外,在这些免疫缺陷小鼠以及野生型小鼠中,V3肽特异性IgG亚类Ab亚型应答中IgG3最高。另外,通过用rBCG-V3J1鼻腔免疫诱导的这种Ag特异性血清IgG Ab具有在体外中和HIV临床分离株的能力。这些结果表明,除了用于预防艾滋病的预防性疫苗以外,鼻rBCG-V3J1系统还可以用作治疗性疫苗。

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