In Vitro Activation of Immune Cells Using Polyanhydride Microspheres: Role of Polymer

According to the NIH, infectious disease remains the second leading case of death worldwide. While current vaccines are excellent at preventing disease due to antibody mediated protection (e.g. neutralizing tetanus toxin and influenza virus), they provide poor protection against diseases where cell mediated immune responses are needed (e.g., tuberculosis). To address this critical need, new vaccine adjuvants are needed that will induce cellular immunity. Polyanhydride microspheres can be used as adjuvants for single dose immunization regimens and may be able to enhance cellular immune responses. This study focused on microspheres composed of the anhydride monomers 1,6-bis(p-carboxyphenoxy)hexane (CPH), sebacic acid (SA) and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG). The in vitro activation of murine bone marrow-derived dendritic cells (DCs) by CPH:SA and CPTEG:CPH microspheres was demonstrated by the increased expression of cell surface molecules and secretion of cytokines. The surface markers tested included those used for antigen presentation (MHCII) and T cell co-stimulation (CD86 and CD40). The ability of CPH:SA and CPTEG:CPH to stimulate DCs was further demonstrated by the increased secretion of IL-6 and IL-12. Altogether, these studies demonstrated that the novel chemistries offered by polyanhydride microspheres are promising candidates for developing improved vaccine-based therapies.