Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Vaccine. 2009 Dec 10;28(1):187-94. doi: 10.1016/j.vaccine.2009.09.101. Epub 2009 Sep 27.
Recent studies have suggested that yeast cell wall components possess adjuvant activities. In the present study, heat-killed whole recombinant Hansenula polymorpha yeast expressing hepatitis B surface antigen (yeast-HBsAg) was generated, and the immune responses elicited by yeast-HBsAg were investigated in mice. The studies showed that yeast-HBsAg as well as yeast greatly promotes the accumulation of immune cells in mouse spleen and contributes to the maturation of dendritic cells (DCs). Yeast-HBsAg not only induces significantly higher antibody responses (including IgG, IgG1 and IgG2a), but also increases the IgG2a/IgG1 ratio, while alum combined with HBsAg (HBsAg+alum) only enhances antibody responses, but not the IgG2a/IgG1 ratio compared to HBsAg alone. Analysis of HBsAg-specific cytokines revealed that yeast-HBsAg is associated with production of both IFN-gamma and IL-4, but neither IFN-gamma nor IL-4 was detected in the HBsAg+alum-immunized group. Moreover, yeast-HBsAg induces potent HBsAg-specific lymphocyte proliferation and Cytotoxic T lymphocyte (CTL) responses. In conclusion, yeast-HBsAg enhances both HBsAg-specific Th1 and Th2 immune responses, while alum only enhances Th2 immune responses, suggesting that yeast-HBsAg may be an ideal candidate for an effective vaccine for the control of chronic hepatitis B virus (HBV) infection.
最近的研究表明,酵母细胞壁成分具有佐剂活性。本研究中,制备了热灭活的、表达乙型肝炎表面抗原的重组汉逊酵母(yeast-HBsAg),并在小鼠中研究了其诱导的免疫应答。结果表明,酵母-HBsAg 和酵母均能显著促进小鼠脾脏中免疫细胞的聚集,并有助于树突状细胞(DCs)的成熟。酵母-HBsAg 不仅诱导了更高的抗体应答(包括 IgG、IgG1 和 IgG2a),而且增加了 IgG2a/IgG1 的比值,而氢氧化铝与 HBsAg (HBsAg+alum)联合应用仅增强了抗体应答,而与单独的 HBsAg 相比,并不增加 IgG2a/IgG1 的比值。对 HBsAg 特异性细胞因子的分析表明,酵母-HBsAg 与 IFN-γ和 IL-4 的产生有关,但在 HBsAg+alum 免疫组中未检测到 IFN-γ或 IL-4。此外,酵母-HBsAg 诱导强烈的 HBsAg 特异性淋巴细胞增殖和细胞毒性 T 淋巴细胞(CTL)应答。总之,酵母-HBsAg 增强了 HBsAg 特异性 Th1 和 Th2 免疫应答,而氢氧化铝仅增强了 Th2 免疫应答,提示酵母-HBsAg 可能是控制慢性乙型肝炎病毒(HBV)感染的有效疫苗的理想候选物。