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

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• 作者：Lu Han ; Jiao Xue ; Luyao Wang ; Ke Peng ; Zhirong Zhang ; Tao Gong ; Xun Sun ; ^{xunsun22@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Gel ; CpG-ODN ; Sustained release ; Vaccine ; Antibody ; Irritation
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：105
• 期：Complete
• 页码：185-194
• 全文大小：4143 K

文摘

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.