RECOMBINANT LISTERIA-MONOCYTOGENES AS A LIVE VACCINE VEHICLE FOR THE INDUCTION OF PROTECTIVE ANTIVIRAL CELL-MEDIATED-IMMUNITY
RECOMBINANT LISTERIA-MONOCYTOGENES AS A LIVE VACCINE VEHICLE FOR THE INDUCTION OF PROTECTIVE ANTIVIRAL CELL-MEDIATED-IMMUNITY
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DOI：
10.1073/pnas.92.9.3987
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发表时间：
1995-04-25
影响因子：
11.1
通讯作者：
MILLER, JF
中科院分区：
文献类型：
--
作者：
SHEN, H;SLIFKA, MK;MILLER, JF
单核细胞增生李斯特菌（Listeria monocytogenes，LM）是一种革兰氏阳性细菌，其能够进入宿主细胞，从内吞囊泡逃逸，在细胞质内繁殖，并直接从细胞扩散到细胞而不遇到细胞外环境。LM进入宿主细胞胞质溶胶的能力允许细菌分泌的蛋白质有效地进入主要组织相容性复合物I类抗原加工和呈递的途径。我们已经建立了一个基因系统的表达和分泌外源抗原的重组菌株，基于稳定的位点特异性整合的表达盒到LM基因组中，LM重组体诱导保护性免疫的能力，对异源病原体与淋巴细胞性脉络丛脑膜炎病毒（LCMV）的证明。表达完整LCMV核蛋白或H-2L（d）限制性核蛋白表位的LM株（aa 118-126）的小鼠。用LM疫苗株免疫小鼠赋予针对LCMV强毒株攻击的保护，否则所述强毒株在幼稚成年小鼠中建立慢性感染。来自接种疫苗的小鼠的CD 8（+）T细胞的体内耗尽废除了它们清除病毒感染的能力，显示保护性抗病毒免疫是由于CD 8（+）T细胞。
Listeria monocytogenes (LM) is a Grampositive bacterium that is able to enter host cells, escape from the endocytic vesicle, multiply within the cytoplasm, and spread directly from cell to cell without encountering the extracellular milieu, The ability of LM to gain access to the host cell cytosol allows proteins secreted by the bacterium to efficiently enter the pathway for major histocompatibility complex class I antigen processing and presentation. We have established a genetic system for expression and secretion of foreign antigens by recombinant strains, based on stable site-specific integration of expression cassettes into the LM genome, The ability of LM recombinants to induce protective immunity against a heterologous pathogen was demonstrated with lymphocytic choriomeningitis virus (LCMV). LM strains expressing the entire LCMV nucleoprotein or an H-2L(d)-restricted nucleoprotein epitope (aa 118-126) were constructed, Immunization of mice with LM vaccine strains conferred protection against challenge with virulent strains of LCMV that otherwise establish chronic infection in naive adult mice, In vivo depletion of CD8(+) T cells from vaccinated mice abrogated their ability to clear viral infection, showing that protective anti-viral immunity was due to CD8(+) T cells.