Oxidized Carbon Nanosphere-Based Subunit Vaccine Delivery System Elicited Robust Th1 and Cytotoxic T Cell Responses

Subunit vaccine is safe and more stable than live vaccine but it has disadvantage in eliciting poor immune response. To develop a subunit vaccine, an effective delivery system targeting the key elements of the protective immune response is a prerequisite. In this study, oxidized carbon nanosphere (OCN) was used as a subunit vaccine delivery system and tuberculosis (TB) was chosen as a model disease. TB is among the deadliest infectious diseases worldwide and an effective vaccine is urgently needed. The ability of OCN to deliver recombinant Mycobacterium tuberculosis (Mtb) proteins, Ag85B and HspX, into bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs) were investigated. For immunization, OCN was mixed with the two TB antigens as well as the adjuvant monophosphoryl lipid A (MPL). The protective efficacy was analyzed in vaccinated mice by aerosol Mtb challenge with virulent strain of Mtb and the bacterial burdens were measured. The results showed that OCN is highly effective in delivery of Mtb proteins into cytosol of BMDMs and BMDCs. Upon immunization, this vaccine formula induced robust Th1 immune response characterized by cytokine profiles from re-stimulated splenocytes and specific antibody titer. More importantly, enhanced cytotoxic CD8⁺ T cell activation was observed. However, it did not reduce bacteria burden in lung and spleen from aerosol Mtb challenge. Taken together, OCN is highly effective in delivery of subunit protein vaccine and induces robust Th1 and CD8⁺ T cell response. This vaccine delivery system is suitable for application in settings where cell-mediated immune response is needed.