Immunostimulatory- Fusogenic and Conventional Liposome Adjuvants Induce Qualitatively and Quantitatively Distinct Innate and Adaptive Immune Responses

An ideal adjuvant should possess both immunostimulatory and antigen delivery properties for simultaneous induction of innate and adaptive immune response to clear pathogens from host. The majority of pharmaceutical based adjuvants currently being used are particle based delivery systems, such as liposome formulations. However, the mechanism of their action is largely unknown. To identify the regulatory gene cascade that triggers the innate immune response following liposome adjuvant injection, we applied microarray based transcriptional profiling of tissue sites (muscle and peritoneum) of mouse injected with conventional (CL) and immunostimulatory fusogenic liposomes (IFL). While CL and IFL induced large number of shared innate immune genes, IFL activated quantitatively and qualitatively stronger immune response than CL. IFL induced upregulation of pro-inflammatory response genes and triggered a rapid influx of antigen presenting cells (APCs) as compared to CL. Comparisonof gene interaction network revealed several fold increase of gene interactions at the injection site with IFL as compared to CL. The induction of innate response by IFL was correlated to strong adaptive response against encapsulated antigen ovalbumin (OVA) indicated by strong T cell proliferation and cytokine production.Notably, CL induced a biased Th2 response whereas IFL favored a predominant Th1 or mixed of Th1/ Th2 response. Our data indicate that IFL induced quantitatively and qualitatively distinct and strong innate immune signals which correlated to strong adaptive immune response. These results provide novel insights into understanding the mechanism of action of liposomes and may be utilized for development of improved liposome based vaccines.