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用表达严重急性呼吸综合征冠状病毒核衣壳蛋白基因的重组复制缺陷型腺病毒载体和DNA质粒对BALB/c小鼠进行比较免疫。

Comparative immunization in BALB/c mice with recombinant replication-defective adenovirus vector and DNA plasmid expressing a SARS-CoV nucleocapsid protein gene.

作者信息

Ma Chunling, Yao Kun, Zhou Feng, Zhu Minsheng

机构信息

Department of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, China.

出版信息

Cell Mol Immunol. 2006 Dec;3(6):459-65.

Abstract

In order to investigate immunogenicity in the induction of humoral and cellular immune responses, severe acute respiratory syndrome associated coronavirus (SARS-CoV)-N gene recombinant replication-defective adenoviral vector, rAd-N, was generated and immunized BALB/c mice in a pcDNA3.1-N prime-rAd-N boost regimen. After humoral and cellular immune response detection, different levels of SARS-CoV N protein specific antibodies and interferon-gamma (IFN-gamma) secretion are shown compared to controls. The humoral immune response was induced more effectively by the DNA priming and recombinant adenovirus boosting regimen. There is a significant difference between heterogeneous and homologous vaccinations. The heterogeneous combinations were all higher than those of the homologous combinations in the induction of anti-N antibody response. Among the three heterogeneous combinations, pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N/rAd-N induced the strongest antibody response. In the induction of IFN-gamma production, the homologous combination of rAd-N/rAd-N/rAd-N/rAd-N was significantly stronger than that of pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N, but was relatively weaker than the heterogeneous combination of pcDAN3.1-N/pcDAN3.1-N/pcDAN3.1-N/rAd-N. This combination was a most efficient immunization regimen in induction of SARS-CoV-N-specific (IFN-gamma) secretion just as the antibody response. These results suggest that DNA immunization followed by recombinant adenovirus boosting could be used as a potential SARS-CoV vaccine.

摘要

为了研究诱导体液免疫和细胞免疫反应中的免疫原性,构建了严重急性呼吸综合征相关冠状病毒(SARS-CoV)-N基因重组复制缺陷型腺病毒载体rAd-N,并采用pcDNA3.1-N初免-rAd-N加强免疫方案对BALB/c小鼠进行免疫。在检测体液免疫和细胞免疫反应后,与对照组相比,显示出不同水平的SARS-CoV N蛋白特异性抗体和干扰素-γ(IFN-γ)分泌。DNA初免和重组腺病毒加强免疫方案能更有效地诱导体液免疫反应。异源和同源疫苗接种之间存在显著差异。在诱导抗N抗体反应方面,异源组合均高于同源组合。在三种异源组合中,pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N/rAd-N诱导的抗体反应最强。在诱导IFN-γ产生方面,rAd-N/rAd-N/rAd-N/rAd-N的同源组合明显强于pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N,但相对弱于pcDAN3.1-N/pcDAN3.1-N/pcDAN3.1-N/rAd-N的异源组合。这种组合在诱导SARS-CoV-N特异性(IFN-γ)分泌方面与抗体反应一样,是一种最有效的免疫方案。这些结果表明,DNA免疫后用重组腺病毒加强免疫可作为一种潜在的SARS-CoV疫苗。

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