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首页> 外文学位 >Humoral and cellular immune responses in RNA viral infections: Immunogenicity of HIV-1, HCV and SARS-CoV candidate vaccines in animal models.
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Humoral and cellular immune responses in RNA viral infections: Immunogenicity of HIV-1, HCV and SARS-CoV candidate vaccines in animal models.

机译：RNA病毒感染中的体液和细胞免疫应答：HIV-1，HCV和SARS-CoV候选疫苗在动物模型中的免疫原性。

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摘要

It is difficult to induce protective immunity against most RNA viruses. However, there is strong evidence that humoral and especially cellular immune responses play crucial roles in the control of established RNA viral infections. Thus, an ideal vaccine should be able to induce strong specific antibody titer as well as a robust T-helper and T-cell cytotoxic response. Here, correlates of protective immunity against HIV-1, HCV and SARS-CoV were assessed.; Monocistronic and polycistronic DNA constructs containing structural HIV-l, and SARS genes were designed. The structural proteins (HIV- gpl20, gag, pol, HCV-core, E1/E2 and SARS-NC) were also expressed, purified and characterized in mammalian and bacterial cell lines. HLA-A2.1 and B6 mice were immunized with different combinations of DNA constructs, recombinant proteins and novel adjuvants. Humoral responses were measured by titrating of specific antibodies and cell-mediated immune responses were identified by Th1/Th2 cytokine expression, lymphocyte proliferation, intracellular cytokine staining, HLA-peptide dimer assay, and ELISPOT. The first study in HIV-1 showed that a combination of DNA single constructs, protein and adjuvant induce a higher immune response compared to the DNA or/and protein alone. In the second HIV-1 approach, a synergistic effect between HIV/HCV antigens was detected that may lead to induction of multi-specific immune responses against both HIV and HCV. In the third study (SARS project), a high level of specific SARS-CD8+ T-cell response was demonstrated in mice that received DNA encoding the SARS-nucleocapsid, protein and XIAP (X-link inhibitor of apoptosis) as an adjuvant.
机译：难以诱导针对大多数RNA病毒的保护性免疫。但是，有强有力的证据表明，体液免疫反应，尤其是细胞免疫反应，在控制已建立的RNA病毒感染中起着至关重要的作用。因此，理想的疫苗应该能够诱导强的特异性抗体滴度以及强大的T辅助和T细胞细胞毒性反应。在这里，评估了针对HIV-1，HCV和SARS-CoV的保护性免疫的相关性。设计了含有结构HIV-1和SARS基因的单顺反子和多顺反子DNA构建体。还在哺乳动物和细菌细胞系中表达，纯化和表征了结构蛋白（HIV-gp120，gag，pol，HCV-core，E1 / E2和SARS-NC）。用DNA构建体，重组蛋白和新型佐剂的不同组合免疫HLA-A2.1和B6小鼠。通过滴定特异性抗体来测量体液反应，并通过Th1 / Th2细胞因子表达，淋巴细胞增殖，细胞内细胞因子染色，HLA肽二聚体测定和ELISPOT鉴定细胞介导的免疫反应。 HIV-1的第一项研究表明，与单独的DNA或/和蛋白质相比，DNA单一构建体，蛋白质和佐剂的组​​合可诱导更高的免疫反应。在第二种HIV-1方法中，检测到HIV / HCV抗原之间的协同效应，这可能导致诱导针对HIV和HCV的多特异性免疫反应。在第三项研究（SARS项目）中，在接受佐剂编码SARS核衣壳，蛋白质和XIAP（凋亡的X链抑制剂）的DNA的小鼠中，证明了高水平的特异性SARS-CD8 + T细胞应答。

著录项

  • 作者

    Azizi, Ali.;

  • 作者单位

    University of Ottawa (Canada).;

  • 授予单位 University of Ottawa (Canada).;
  • 学科 Biology Virology.; Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2006
  • 页码 142 p.
  • 总页数 142
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 预防医学、卫生学;
  • 关键词

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