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标题:Animal models paving the way for clinical trials of attenuated Salmonella enterica serovar Typhi live oral vaccines and live vectors
时间:2020-01-15 19:36:33
DOI:10.1016/s0264-410x(02)00472-3
作者:Marcela F Pasetti;Myron M Levine;Marcelo B Sztein
关键词:Salmonella;Live vector vaccines;Animal models
出版源: 《Vaccine》 ,2003 ,21 (5-6) :401-418
摘要:Attenuated Salmonella enterica serovar Typhi ( S. Typhi) strains can serve as safe and effective oral vaccines to prevent typhoid fever and as live vectors to deliver foreign antigens to the immune system, either by the bacteria expressing antigens through prokaryotic expression plasmids or by delivering foreign genes carried on eukaryotic expression systems (DNA vaccines). The practical utility of such live vector vaccines relies on achieving a proper balance between minimizing the vaccine’s reactogenicity and maximizing its immunogenicity. To advance to clinical trials, vaccine candidates need to be pre-clinically evaluated in relevant animal models that attempt to predict what their safety and immunogenicity profile will be when administered to humans. Since S. Typhi is a human-restricted pathogen, a major obstacle that has impeded the progress of vaccine development has been the shortcomings of the animal models available to assess vaccine candidates. In this review, we summarize the usefulness of animal models in the assessment of the degree of attenuation and immunogenicity of novel attenuated S. Typhi strains as vaccine candidates for the prevention of typhoid fever and as live vectors in humans.
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目录:
  • Animal models paving the way for clinical trials of attenuated Salmonella enterica serovar Typhi live oral vaccines and live vectors
    • Introduction
    • Typhoid fever: pathogenesis and immunity
      • Insights from the chimpanzee model
      • Insights from the mouse typhoid model
      • An understanding of the pathogenesis and immunity of human typhoid infection based on a composite of data from human and animal model infections
    • Attenuated Salmonella strains as live oral vaccines and live vectors
      • The need for a typhoid vaccine and the potential advantages of S. Typhi as a live vector
      • Identifying attenuated Salmonella strains
    • Animal models to assess the degree of attenuation and protective efficacy of candidate live S. Typhi vaccines
      • Intraperitoneal inoculation of mice with S. Typhi and hog gastric mucin to evaluate attenuation and efficacy of typhoid vaccines
    • Results of Phases 1 and 2 clinical trials with engineered attenuated S. Typhi strains
    • Animal models to assess the immunogenicity of attenuated Salmonella live vector vaccines expressing foreign antigens
      • Salmonella live vector strains in mice
      • Mouse model of intranasal immunization with S. Typhi live vectors
        • Development and applications of the model
        • Characterization of the murine intranasal model
    • Clinical trials of attenuated S. Typhi live vector vaccines expressing foreign antigens
      • Ty21a-based live vector vaccines
      • Live vector vaccines based on other attenuated S. Typhi strains
    • Animal models to assess the immunogenicity of attenuated Salmonella live vector vaccines carrying eukaryotic expression systems encoding foreign antigens (i.e. DNA vaccines)
      • Salmonella live vectors carrying DNA vaccines
      • S. Typhi live vectors carrying DNA vaccines
    • Bridging the gap: from animal models to clinical trials
    • Acknowledgements
    • References

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