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首页> 外文期刊>Developmental Immunology: Journal of Immunology Research >Immunogenicity and Protective Efficacy against Murine Tuberculosis of a Prime-Boost Regimen with BCG and a DNA Vaccine Expressing ESAT-6 and Ag85A Fusion Protein
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Immunogenicity and Protective Efficacy against Murine Tuberculosis of a Prime-Boost Regimen with BCG and a DNA Vaccine Expressing ESAT-6 and Ag85A Fusion Protein

机译：具有BCG和表达ESAT-6和Ag85A融合蛋白的DNA疫苗的初免-加强方案的小鼠结核病的免疫原性和保护作用。

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Heterologous prime-boost regimens utilizing BCG as a prime vaccine probably represent the best hope for the development of novel tuberculosis (TB) vaccines. In this study, we examined the immunogenicity and protective efficacy of DNA vaccine (pcD685A) expressing the fusion protein of Ag85A and ESAT-6 (r685A) and its booster effects in BCG-immunized mice. The recombinant r685A fusion protein stimulated higher level of antigen-specific IFN-γrelease in tuberculin skin test- (TST-) positive healthy household contacts of active pulmonary TB patients than that in TST-negative population. Vaccination of C57BL/6 mice with pcD685A resulted in significant protection against challenge with virulentMycobacterium tuberculosisH37Rv when compared with the control group. Most importantly, pcD685A could act as a BCG booster and amplify Th1-type cell-mediated immunity in the lung of BCG-vaccinated mice as shown the increased expression of IFN-γ. The most significant reduction in bacterial load of both spleen and lung was obtained in mice vaccinated with BCG prime and pcD685A DNA booster when compared with BCG or pcD685A alone. Thus, our study indicates that pcD685A may be an efficient booster vaccine against TB with a strong ability to enhance prior BCG immunity.
机译：利用卡介苗作为主要疫苗的异源初免-加强疗法可能代表了新型结核病（TB）疫苗开发的最大希望。在这项研究中，我们检查了表达Ag85A和ESAT-6（r685A）融合蛋白的DNA疫苗（pcD685A）的免疫原性和保护作用及其在BCG免疫小鼠中的增强作用。重组r685A融合蛋白在活动性肺结核患者的结核菌素皮肤试验阳性（TST-）阳性健康家庭接触中刺激的抗原特异性IFN-γ释放水平高于TST阴性人群。与对照组相比，用pcD685A疫苗接种C57BL / 6小鼠可显着抵抗强力结核分枝杆菌H37Rv的攻击。最重要的是，pcD685A可以作为BCG增强剂，并在接种BCG的小鼠肺中增强Th1型细胞介导的免疫力，这表明IFN-γ的表达增加。与单独的BCG或pcD685A相比，在接种了BCG初免和pcD685A DNA加强免疫的小鼠中，脾脏和肺部细菌载量的减少幅度最大。因此，我们的研究表明pcD685A可能是针对结核病的有效加强疫苗，具有增强先前BCG免疫力的强大能力。

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