PROTECTIVE IMMUNE-RESPONSES INDUCED BY SECRETION OF A CHIMERIC SOLUBLE-PROTEIN FROM A RECOMBINANT MYCOBACTERIUM-BOVIS BACILLUS-CALMETTE-GUERIN VECTOR CANDIDATE VACCINE FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN SMALL ANIMALS
PROTECTIVE IMMUNE-RESPONSES INDUCED BY SECRETION OF A CHIMERIC SOLUBLE-PROTEIN FROM A RECOMBINANT MYCOBACTERIUM-BOVIS BACILLUS-CALMETTE-GUERIN VECTOR CANDIDATE VACCINE FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN SMALL ANIMALS
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DOI：
10.1073/pnas.92.23.10693
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发表时间：
1995-11-07
影响因子：
11.1
通讯作者：
YAMAZAKI, S
中科院分区：
文献类型：
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作者：
HONDA, M;MATSUO, K;YAMAZAKI, S
人免疫缺陷病毒（human immunodeficiency virus，HIV）V3主要中和表位的重组卡介苗（MycobacteriumbovisbacillusCalmette-Guerin，BCG）载体疫苗能诱导机体产生针对该表位的免疫应答，预防HIV感染。利用日本HIV-1的共有序列，我们通过选择合适的载体蛋白插入位点成功构建了嵌合蛋白分泌载体，并在BCG中建立了主要中和决定簇（PND）-肽分泌系统。重组卡介苗（rBCG）接种豚鼠后，首先通过对PND肽的迟发型超敏反应（DTH）进行筛选，然后通过全身途径被动转移DTH，进一步用rBCG免疫小鼠，诱导细胞毒性T淋巴细胞。豚鼠免疫抗血清对PND肽和中和HIVMN显示出升高的滴度，并且接种豚鼠的血清IgG的施用有效地完全阻断胸腺/肝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，证明免疫血清IgG可中和与中和序列基序匹配的HIV原代田间分离株。这些数据支持这样的想法，即抗原分泌rBCG系统可以用作HIV疫苗开发的工具。
A recombinant Mycobacterium bovis bacillus Calmette-Guerin (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 fell-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.