An injectable, low-toxicity phospholipid-based phase separation gel that induces strong and persistent immune responses in mice

作者：Han, Lu; Xue, Jiao; Wang, Luyao; Peng, Ke; Zhang, Zhirong; Gong, Tao; Sun, Xun^*

来源：Biomaterials, 2016, 105: 185-194.

DOI：10.1016/j.biomaterials.2016.08.007

• Gel
• CpG-ODN
• Sustained release
• Vaccine
• Antibody
• Irritation

Sustained antigen delivery using incomplete Freund's adjuvant (IFA) can induce strong, long-term immune response, but it can also cause severe side effects. Here we describe an injectable, phospholipid-based phase separation gel (PPSG) that readily transforms in situ into a drug depot. PPSG loaded with the model antigen ovalbumin (OVA) supported sustained OVA release in mice that lasted nearly one month. Immunizing mice with a single injection of PPSG/OVA elicited a strong and persistent increase in titers of OVA-specific IgG, IgG1 and IgG2a. Co-administering CpG-ODN further increased antibody titers. Such co-administration recruited dendritic cells to injection sites and activated dendritic cells in the draining lymph nodes. Moreover, immunization with PPSG/OVA/CpG resulted in potent memory antibody responses and high frequency of memory T cells. Remarkably, PPSG/OVA/CpG was associated with much lower toxicity at injection sites than IFA/OVA/CpG, and it showed no systemic toxicity such as to lymph nodes or spleen. These findings illustrate the potential of injectable PPSG for sustained, minimally toxic delivery of antigens and adjuvants.

• 出版日期2016-10
• 单位四川大学