Sawutdeechaikul Pritsana, Cia Felipe, Bancroft Gregory, Wanichwecharungruang Supason, Sittplangkoon Chutamath, Palaga Tanapat
Graduate Program in Microbiology and Microbial Technology, Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
Center of Excellence in Immune-mediated Diseases, Chulalongkorn University, Bangkok 10330, Thailand.
J Microbiol Biotechnol. 2019 Mar 28;29(3):489-499. doi: 10.4014/jmb.1809.09049.
Subunit vaccines are safer and more stable than live vaccines although they have the disadvantage of 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 nanospheres (OCNs) were 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 OCNs to deliver recombinant (Mtb) proteins, Ag85B and HspX, into bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs) was investigated. For immunization, OCNs were 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 a virulent strain of Mtb and the bacterial burdens were measured. The results showed that OCNs are highly effective in delivering Mtb proteins into the cytosol of BMDMs and BMDCs. Upon immunization, this vaccine formula induced robust Th1 immune response characterized by cytokine profiles from restimulated splenocytes and specific antibody titer. More importantly, enhanced cytotoxic CD8⁺ T cell activation was observed. However, it did not reduce the bacteria burden in the lung and spleen from the aerosol Mtb challenge. Taken together, OCNs are highly effective in delivering subunit protein vaccine and induce robust Th1 and CD8⁺ T cell response. This vaccine delivery system is suitable for application in settings where cell-mediated immune response is needed.
亚单位疫苗比活疫苗更安全、更稳定，尽管它们有引发免疫反应不佳的缺点。要开发亚单位疫苗，一个针对保护性免疫反应关键要素的有效递送系统是先决条件。在本研究中，氧化碳纳米球（OCNs）被用作亚单位疫苗递送系统，并选择结核病（TB）作为模型疾病。结核病是全球最致命的传染病之一，迫切需要一种有效的疫苗。研究了OCNs将重组结核分枝杆菌（Mtb）蛋白Ag85B和HspX递送至骨髓来源的巨噬细胞（BMDMs）和树突状细胞（BMDCs）的能力。为了进行免疫接种，将OCNs与两种结核抗原以及佐剂单磷酰脂质A（MPL）混合。通过用毒力强的结核分枝杆菌菌株进行气溶胶结核分枝杆菌攻击对接种疫苗的小鼠的保护效果进行了分析，并测量了细菌载量。结果表明，OCNs在将结核分枝杆菌蛋白递送至BMDMs和BMDCs的细胞质中非常有效。免疫接种后，这种疫苗配方诱导了以再刺激脾细胞的细胞因子谱和特异性抗体滴度为特征的强大的Th1免疫反应。更重要的是，观察到细胞毒性CD8⁺T细胞活化增强。然而，它并没有降低气溶胶结核分枝杆菌攻击后肺和脾中的细菌载量。综上所述，OCNs在递送亚单位蛋白疫苗方面非常有效，并诱导强大的Th1和CD8⁺T细胞反应。这种疫苗递送系统适用于需要细胞介导免疫反应的环境。
