title: An injectable, low-toxicity phospholipid-based phase separation gel that induces strong and persistent immune responses in mice.
abstract: 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.
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, PR China.
authors: Lu
authors: L
authors: Han
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, PR China.
authors: Jiao
authors: J
authors: Xue
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, PR China.
authors: Luyao
authors: L
authors: Wang
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, PR China.
authors: Ke
authors: K
authors: Peng
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, PR China.
authors: Zhirong
authors: Z
authors: Zhang
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, PR China.
authors: Tao
authors: T
authors: Gong
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, PR China. Electronic address: xunsun22@gmail.com.
authors: Xun
authors: X
authors: Sun
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007267:Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D044367:Phase Transition; D010743:Phospholipids / Q000737:chemistry* / Q000633:toxicity; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D001323:Autoantibodies; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D010743:Phospholipids
keywords: Antibody; CpG-ODN; Gel; Irritation; Sustained release; Vaccine