Hiroi T, Goto H, Someya K, Yanagita M, Honda M, Yamanaka N, Kiyono H
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
J Immunol. 2001 Nov 15;167(10):5862-7. doi: 10.4049/jimmunol.167.10.5862.
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.
在抗HIV疫苗策略中，卡介苗（BCG），一种牛分枝杆菌的减毒活菌株，被认为是黏膜递送疫苗抗原的潜在载体之一。我们分析了用可分泌HIV V3主要中和表位的重组卡介苗载体疫苗（rBCG-V3J1）经鼻免疫诱导的抗原特异性抗体反应。小鼠每周用rBCG-V3J1（10微克）经鼻免疫3次。初次免疫后4周，血清中出现高滴度的V3J1特异性IgG抗体。经鼻免疫后，在没有任何加强免疫的情况下，这些高水平的HIV特异性血清IgG反应维持了超过12个月。在从经鼻接种小鼠的脾脏、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。经鼻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、持续时间长的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，IgG3在V3肽特异性IgG亚类抗体反应中最高。此外，经鼻用rBCG-V3J1免疫诱导的这种抗原特异性血清IgG抗体在体外具有中和HIV临床分离株的能力。这些结果表明，经鼻rBCG-V3J1系统除了可作为预防艾滋病的疫苗外，还可能用作治疗性疫苗。
