Ito H, Ando T, Nakamura M, Ishida H, Kanbe A, Kobiyama K, Yamamoto T, Ishii K J, Hara A, Seishima M, Ishikawa T
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Gifu, Japan.
Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
J Viral Hepat. 2017 Feb;24(2):155-162. doi: 10.1111/jvh.12629. Epub 2016 Nov 3.
A persistent hepatitis B virus (HBV) infection is characterized by a lack of or a weak immune response to HBV, which may be reflective of tolerance to HBV. Efficient induction of HBV-specific immune response leads to the clearance of HBV in patients with a chronic HBV infection. CpG oligodeoxynucleotides (ODN) has a powerful adjuvant effect in HBV vaccination. A recent report demonstrated that the immunization by B/K CpG ODN (K3) wrapped by the nonagonistic Dectin-1 ligand, schizophyllan (SPG), namely K3-SPG, was more effective in the induction of antigen-specific immune response than that by K3. In this study, we examined the efficacy of K3-SPG as a HBV vaccine adjuvant. Wild-type (WT) mice and HBV transgenic (HBV-Tg) mice were subcutaneously immunized with hepatitis B surface antigen (HBsAg) alone, HBsAg and K3, or HBsAg and K3-SPG. The vaccination with HBsAg and K3-SPG significantly enhanced humoral and cellular immune response to HBV antigen compared to the other vaccinations in WT and HBV-Tg mice. K3-SPG induced the accumulation of dendritic cells (DCs) into draining lymph node and the activation of DCs. The expression of cytokines and chemokines related to Th1 and Th2 responses was upregulated after the vaccination including with K3-SPG. In conclusion, these results indicated that the vaccination using K3-SPG may overcome tolerance even in patients with chronic HBV infection.
持续性乙型肝炎病毒（HBV）感染的特征是对HBV缺乏免疫反应或免疫反应较弱，这可能反映了对HBV的耐受性。有效诱导HBV特异性免疫反应可导致慢性HBV感染患者清除HBV。CpG寡脱氧核苷酸（ODN）在HBV疫苗接种中具有强大的佐剂作用。最近的一份报告表明，由非激动性的Dectin-1配体裂褶菌多糖（SPG）包裹的B/K CpG ODN（K3）进行免疫，即K3-SPG，在诱导抗原特异性免疫反应方面比K3更有效。在本研究中，我们检测了K3-SPG作为HBV疫苗佐剂的效果。将野生型（WT）小鼠和HBV转基因（HBV-Tg）小鼠分别皮下注射单独的乙型肝炎表面抗原（HBsAg）、HBsAg和K3，或HBsAg和K3-SPG。与WT和HBV-Tg小鼠的其他疫苗接种相比，用HBsAg和K3-SPG进行疫苗接种显著增强了对HBV抗原的体液免疫和细胞免疫反应。K3-SPG诱导树突状细胞（DCs）在引流淋巴结中积聚并激活DCs。接种疫苗（包括K3-SPG）后，与Th1和Th2反应相关的细胞因子和趋化因子的表达上调。总之，这些结果表明，使用K3-SPG进行疫苗接种甚至可能克服慢性HBV感染患者的耐受性。
