University of Chinese Academy of Sciences, Beijing 100049, China.
Key Laboratory of Biopharmaceutical Production & Formulation Engineering, PLA and State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
Mar Drugs. 2017 Jul 26;15(8):236. doi: 10.3390/md15080236.
Chitosan oligosaccharides (COS), the degraded products of chitosan, have been demonstrated to have versatile biological functions. In primary studies, it has displayed significant adjuvant effects when mixed with other vaccines. In this study, chitosan oligosaccharides with different deacetylation degrees were prepared and conjugated to porcine circovirus type 2 (PCV2) subunit vaccine to enhance its immunogenicity. The vaccine conjugates were designed by the covalent linkage of COSs to PCV2 molecules and administered to BALB/c mice three times at two-week intervals. The results indicate that, as compared to the PCV2 group, COS-PCV2 conjugates remarkably enhanced both humoral and cellular immunity against PCV2 by promoting lymphocyte proliferation and initiating a mixed T-helper 1 (Th1)/T-helper 2 (Th2) response, including raised levels of PCV2-specific antibodies and an increased production of inflammatory cytokines. Noticeably, with the increasing deacetylation degree, the stronger immune responses to PCV2 were observed in the groups with COS-PCV2 vaccination. In comparison with NACOS (chitin oligosaccharides)-PCV2 and LCOS (chitosan oligosaccharides with low deacetylation degree)-PCV2, HCOS (chitosan oligosaccharides with high deacetylation degree)-PCV2 showed the highest adjuvant effect, even comparable to that of PCV2/ISA206 (a commercialized adjuvant) group. In summary, COS conjugation might be a viable strategy to enhance the immune response to PCV2 subunit vaccine, and the adjuvant effect was positively correlated with the deacetylation degree of COS.
壳寡糖（COS）是壳聚糖的降解产物，具有多种生物学功能。在初步研究中，它与其他疫苗混合使用时具有显著的佐剂效应。在这项研究中，制备了不同脱乙酰度的壳寡糖，并将其与猪圆环病毒 2 型（PCV2）亚单位疫苗偶联，以增强其免疫原性。该疫苗偶联物通过 COS 与 PCV2 分子的共价连接设计，并在两周的间隔内三次施用于 BALB/c 小鼠。结果表明，与 PCV2 组相比，COS-PCV2 缀合物通过促进淋巴细胞增殖并引发混合 T 辅助 1（Th1）/T 辅助 2（Th2）反应，显著增强了针对 PCV2 的体液和细胞免疫，包括提高了 PCV2 特异性抗体水平和增加了炎症细胞因子的产生。值得注意的是，随着脱乙酰度的增加，COS 疫苗接种组对 PCV2 的免疫反应更强。与 NACOS（壳聚糖寡糖）-PCV2 和 LCOS（低脱乙酰度壳聚糖寡糖）-PCV2 相比，HCOS（高脱乙酰度壳聚糖寡糖）-PCV2 表现出最高的佐剂效应，甚至可与 PCV2/ISA206（一种商业化佐剂）组相媲美。总之，COS 缀合可能是增强 PCV2 亚单位疫苗免疫反应的可行策略，并且佐剂效应与 COS 的脱乙酰度呈正相关。
