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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Rabies virus nucleoprotein as a carrier for foreign antigens.
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Rabies virus nucleoprotein as a carrier for foreign antigens.

机译:狂犬病病毒核蛋白可作为外来抗原的载体。

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摘要

Rabies virus (RV) nucleoprotein (N) tightly encapsidates the genomic and antigenomic RNA of RV to form the viral ribonucleoprotein (RNP) complex. Antigens, such as N, presented in a highly organized structure are sufficient and even desirable to activate B cells to proliferate and produce antibodies. In addition to activating B cells to proliferate, it has been shown that RV N in the RNP complex induces potent T helper cell responses resulting in long-lasting and strong humoral immune responses against RV. The possibility to systematically incorporate foreign genes into the genome of RV and produce a recombinant virus allows us to examine whether the immunogenicity of foreign antigens can be enhanced by incorporation into the RV RNP structure. To test this hypothesis we constructed a recombinant RV expressing a RV N-GFP fusion protein. The chimeric N-GFP fusion protein was efficiently expressed and incorporated into RV RNP and virions. Moreover, the recombinant RNP induces a strong humoral immune response against GFP in mice. In contrast, mice inoculated with GFP alone or a combination of wild-type RV RNPs and GFP did not trigger any GFP-specific humoral responses using the same immunization schedule. These data indicate the usefulness of RV-based vectors as killed vaccines against other infectious diseases.
机译:狂犬病病毒(RV)核蛋白(N)紧密包裹着RV的基因组和反基因组RNA,形成病毒核糖核蛋白(RNP)复合体。呈高度组织化结构的抗原(例如N)足以激活B细胞增殖并产生抗体。除了激活B细胞增殖外,已显示RNP复合物中的RV N诱导有效的T辅助细胞反应,导致针对RV的持久而强烈的体液免疫反应。系统性地将外源基因整合到RV基因组中并产生重组病毒的可能性使我们能够检查是否可以通过整合到RV RNP结构中来增强外源抗原的免疫原性。为了检验该假设,我们构建了表达RV N-GFP融合蛋白的重组RV。嵌合的N-GFP融合蛋白被有效地表达并掺入RV RNP和病毒体中。而且,重组RNP在小鼠中诱导针对GFP的强体液免疫应答。相比之下,单独接种GFP或野生型RV RNP和GFP组合接种的小鼠,在使用相同的免疫方案后并未触发任何GFP特异性体液反应。这些数据表明基于RV的载体作为针对其他传染病的灭活疫苗的有用性。

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