Characterization of immune response towards modified Coxsackie B virus-like particle vaccine in a murine model

Abstract

Abstract Coxsackievirus Bs (CVBs) are common human RNA viruses that belong to the enterovirus genus of Picornaviridae. Most commonly, infections with these viruses manifest with mild flu-like symptoms. However, CVBs are also known to cause severe diseases, including aseptic meningitis, myocarditis, and chronic dilated cardiomyopathy (DCM), encephalitis, pancreatitis, and hand-foot-and-mouth disease. In this study, we aimed for a versatile characterization of a modified CVB virus-like particle vaccine in a murine model. The modified CVB-VLP was produced using baculovirus-insect cell production platform. Purified and characterized vaccine was administered to mice via s.c. or i.m. routes, either with or without an adjuvant. Immunological characterization of vaccine response included both humoral and cellular characterization. Antigen-specific IgG levels and neutralizing antibodies in the sera were measured to determine the humoral immune response. To characterize the cellular immunity, activation markers of the lymphocytes were identified using flow cytometry. Additionally, the cytokine secretion of the stimulated splenocytes was determined with FluoroSpot assay. The modified CVB-VLP induced high levels of IgG and neutralizing antibodies in the sera of vaccinated mice. Further, the in vitro stimulation of splenocytes induced activation of mainly CD4+ T-cells, and adjuvanted vaccine induced a significant production level of IFN-γ and IL-2. These results indicate that the virus-like particle combined with an adjuvant is a promising vaccine candidate. In addition, our current challenge study with coxsackie B1 virus will shed us more insight on the protective role of this vaccine. Supported by grants from Finnish Foundations (Instrumentarium Science Foundation, Paulo Foundation and Ida Montini Foundation)