β-Glucan schizophyllan (SPG) and CpG oligonucleotides (ODNs) can form a complex (denoted by CpG-dA400/SPG), which drastically induces immune-response owing to a combination of immunocyte-targeting delivery due to SPG and immunostimulative CpG ODN. We crosslinked CpG-dA400/ SPG by adding cCpG-dA400/SPG to obtain larger particles than the original one by using cCpGCpG hybridization, where cCpG denotes the complementary sequence of CpG. The crosslink particles showed higher immune stimulation and can thus be used as a more potent vaccine adjuvant than CpG-dA400/ SPG itself. © 2014 The Chemical Society of Japan.