Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Oxidized Carbon Nanosphere-Based Subunit Vaccine Delivery System Elicited Robust Th1 and Cytotoxic T Cell Responses

  • Sawutdeechaikul, Pritsana (Graduate Program in Microbiology and Microbial Technology, Department of Microbiology, Faculty of Science, Chulalongkorn University) ;
  • Cia, Felipe (Department of Immunology and Infection, London School of Hygiene and Tropical Medicine) ;
  • Bancroft, Gregory J. (Department of Immunology and Infection, London School of Hygiene and Tropical Medicine) ;
  • Wanichwecharungruang, Supason (Center of Excellence in Materials and Bio-Interfaces, Chulalongkorn University and Department of Chemistry, Faculty of Science, Chulalongkorn University) ;
  • Sittplangkoo, Chutamath (Center of Excellence in Immune-mediated Diseases, Chulalongkorn University) ;
  • Palaga, Tanapat (Graduate Program in Microbiology and Microbial Technology, Department of Microbiology, Faculty of Science, Chulalongkorn University)
  • Received : 2018.09.25
  • Accepted : 2019.01.17
  • Published : 2019.03.28
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Abstract

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 Mycobacterium tuberculosis (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.

Keywords

References

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