Extracellular matrix from porcine small intestinal submucosa as immune adjuvants (52.21)

Abstract

Abstract Porcine small intestinal submucosa (SIS) of Cook Biotech is widely used in tissue remodeling. It also proved safe and effective in enhancing efficacy of a prostate cancer vaccine. In this study, we compared SIS-adjuvanticity with alum’s in mobilizing innate immunity via inflammasomes, and in boosting antibody response to soluble proteins, ovalbumin, and a hapten-protein conjugate, phthalate-KLH. This evaluation carried out in BALB/c, C57Bl/6 and lupus-prone NZB/WF1 mice was done by both Intraperitoneal and subcutaneous routes of immunization. Methods involved determination of antibody titer, isotyping, microarray profiling of cytokines and chemokines and qPCR of inflammasomes-related genes. Results clearly highlighted the difference between SIS and alum. SIS provoked neither pro-inflammatory cytokines (IL-6, IL-1β, and TNFα) nor NLRP3 inflammasomes as alum did, but it did up-regulate IL4 and CD30-ligand. SIS also activated chemotactic factors LIX and KC (neutrophil chemotactic factors), MCP 1 (monocyte chemotactic factors), MCSF and MIP 1-α (macrophage chemotactic factor) and Lympotactin, albeit a little less than Alum. SIS, however, was as effective as alum in engendering lasting and specific antibody responses, primarily of IgG1 type, but proved inconsequential in induction of anti-DNA response or renal pathology. In conclusion, although both alum and SIS induced Th2 type immune response, SIS was much less inflammatory than alum.