Honda M, Matsuo K, Nakasone T, Okamoto Y, Yoshizaki H, Kitamura K, Sugiura W, Watanabe K, Fukushima Y, Haga S, Katsura Y, Tasaka H, Komuro K, Yamada T, Asano T, Yamazaki A, Yamazaki S
AIDS Research Center, National Institute of Health, Tokyo, Japan.
Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10693-7. doi: 10.1073/pnas.92.23.10693.
A recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) vector-based vaccine that secretes the V3 principal neutralizing epitope of human immunodeficiency virus (HIV) could induce immune response to the epitope and prevent the viral infection. By using the Japanese consensus sequence of HIV-1, we successfully constructed chimeric protein secretion vectors by selecting an appropriate insertion site of a carrier protein and established the principal neutralizing determinant (PND)-peptide secretion system in BCG. The recombinant BCG (rBCG)-inoculated guinea pigs were initially screened by delayed-type hypersensitivity (DTH) skin reactions to the PND peptide, followed by passive transfer of the DTH by the systemic route. Further, immunization of mice with the rBCG resulted in induction of cytotoxic T lymphocytes. The guinea pig immune antisera showed elevated titers to the PND peptide and neutralized HIVMN, and administration of serum IgG from the vaccinated guinea pigs was effective in completely blocking the HIV infection in thymus/liver transplanted severe combined immunodeficiency (SCID)/hu or SCID/PBL mice. In addition, the immune serum IgG was shown to neutralize primary field isolates of HIV that match the neutralizing sequence motif by a peripheral blood mononuclear cell-based virus neutralization assay. The data support the idea that the antigen-secreting rBCG system can be used as a tool for development of HIV vaccines.
一种基于重组牛分枝杆菌卡介苗（BCG）载体的疫苗，可分泌人类免疫缺陷病毒（HIV）的V3主要中和表位，能诱导针对该表位的免疫反应并预防病毒感染。通过使用HIV-1的日本共识序列，我们通过选择载体蛋白的合适插入位点成功构建了嵌合蛋白分泌载体，并在卡介苗中建立了主要中和决定簇（PND）-肽分泌系统。对接种重组卡介苗（rBCG）的豚鼠，首先通过对PND肽的迟发型超敏反应（DTH）皮肤反应进行初步筛选，然后通过全身途径进行DTH的被动转移。此外，用rBCG免疫小鼠可诱导细胞毒性T淋巴细胞。豚鼠免疫抗血清对PND肽的滴度升高并中和了HIVMN，接种疫苗的豚鼠血清IgG的给药有效地完全阻断了胸腺/肝脏移植的严重联合免疫缺陷（SCID）/hu或SCID/PBL小鼠中的HIV感染。此外，通过基于外周血单核细胞的病毒中和试验表明，免疫血清IgG可中和与中和序列基序匹配的HIV原发性现场分离株。这些数据支持了抗原分泌性rBCG系统可作为开发HIV疫苗工具的观点。
