结核分枝杆菌抗原重组酿酒酵母免疫诱导小鼠特异性免疫应答

The Vaccination with Saccharomyces cerevisiae Recombined with Mycobacterium tuberculosis Antigens Induces Specific Immunoresponsesin Mice

近年来基于重组酿酒酵母全细胞的新型疫苗研究报道不断出现。以结核杆菌重要保护抗原ESAT6和Ag85B为对象,采用p HR酿酒酵母表达系统,构建了两种分别表达ESAT6-Ag85B(EA)和IFN-γ-ESAT6-Ag85B(IEA)融合抗原的重组酿酒酵母Yeast-EA和Yeast-IEA。重组酵母以皮下注射方式免疫小鼠后,小鼠产生高水平Ag85B特异性抗体,淋巴细胞分泌IFN-γ、IL-2等细胞因子,无IL-4产生,发生Th1型细胞免疫应答,其中Yeast-IEA效应更强,优于传统的BCG疫苗。实验证实重组酵母能够刺激树突状细胞的成熟分化。研究结果显示结核分枝杆菌抗原重组酿酒酵母全细胞疫苗具有发展成为新型抗结核疫苗的潜力。

Recently there were increasing reports about vaccines based on whole recombinant Saccharomyces cerevisiae. Mycobacterium tuberculosis （Mtb） protective antigens ESAT6 and Ag85B against tuberculosis were selected to be expressed in S. cerevisiae with pHR expression system. Two yeasts producing fusion proteins ESTA6-Ag85B （EA） and IFN-γ-ESAT6-Ag85B（IEA） respectively were constructed and the immune responses elicited by the recombinant yeasts were investigated in mice. Injection of mice subcutaneously with the recombinant yeasts induced Ag85B-specific IgG in high level and Thl immune responses associated with IFN-γ and IL-2 secretion and no IL-4 production. Compared to BCG, Yeast-IEA vaccination stimulated significantly stronger immune response. It was confirmed that yeast could activated dendritic cells maturation with upregulation of co-stimulatory molecules and MHC molecules. The results suggest that the whole recombinant yeast （ Yeast- IEA） may be an attractive candidate of vaccines against tuberculosis.