PMID- 30691253 OWN - NLM STAT- MEDLINE DCOM- 20190426 LR - 20190426 IS - 1738-8872 (Electronic) IS - 1017-7825 (Linking) VI - 29 IP - 3 DP - 2019 Mar 28 TI - Oxidized Carbon Nanosphere-Based Subunit Vaccine Delivery System Elicited Robust Th1 and Cytotoxic T Cell Responses. PG - 489-499 LID - 10.4014/jmb.1809.09049 [doi] AB - 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. FAU - Sawutdeechaikul, Pritsana AU - Sawutdeechaikul P AD - Graduate Program in Microbiology and Microbial Technology, Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand. AD - Center of Excellence in Immune-mediated Diseases, Chulalongkorn University, Bangkok 10330, Thailand. FAU - Cia, Felipe AU - Cia F AD - Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. FAU - Bancroft, Gregory AU - Bancroft G AD - Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. FAU - Wanichwecharungruang, Supason AU - Wanichwecharungruang S AD - Center of Excellence in Materials and Bio-Interfaces, Chulalongkorn University and Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand. FAU - Sittplangkoon, Chutamath AU - Sittplangkoon C AD - Center of Excellence in Immune-mediated Diseases, Chulalongkorn University, Bangkok 10330, Thailand. AD - Graduate Program in Biotechnology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand 10330. FAU - Palaga, Tanapat AU - Palaga T AD - Graduate Program in Microbiology and Microbial Technology, Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand. AD - Center of Excellence in Immune-mediated Diseases, Chulalongkorn University, Bangkok 10330, Thailand. AD - Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. AD - Center of Excellence in Materials and Bio-Interfaces, Chulalongkorn University and Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand. LA - eng PT - Journal Article PL - Korea (South) TA - J Microbiol Biotechnol JT - Journal of microbiology and biotechnology JID - 9431852 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antigens, Bacterial) RN - 0 (Bacterial Proteins) RN - 0 (Cytokines) RN - 0 (HspX protein, Mycobacterium tuberculosis) RN - 0 (Tuberculosis Vaccines) RN - 0 (Vaccines, Attenuated) RN - 0 (Vaccines, Subunit) RN - 0 (Vaccines, Synthetic) RN - 7440-44-0 (Carbon) RN - EC 2.3.- (Acyltransferases) RN - EC 2.3.1.- (antigen 85B, Mycobacterium tuberculosis) SB - IM MH - Acyltransferases/genetics MH - Adjuvants, Immunologic MH - Administration, Mucosal MH - Animals MH - Antigens, Bacterial/genetics/immunology MH - Bacterial Proteins/genetics/immunology MH - Bone Marrow MH - Carbon/*chemistry MH - Cytokines/metabolism MH - Dendritic Cells/drug effects MH - Disease Models, Animal MH - Drug Delivery Systems/*methods MH - Female MH - Immunity, Cellular MH - Immunization MH - Lung/microbiology MH - Macrophages/drug effects MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mycobacterium tuberculosis/pathogenicity MH - Nanospheres/*chemistry MH - Spleen/microbiology MH - T-Lymphocytes, Cytotoxic/*immunology MH - Th1 Cells/drug effects MH - Tuberculosis/*prevention & control MH - *Tuberculosis Vaccines MH - Vaccines, Attenuated/administration & dosage/immunology MH - Vaccines, Subunit/administration & dosage/*chemistry/*immunology MH - Vaccines, Synthetic OTO - NOTNLM OT - Carbon nanosphere OT - cytotoxic T lymphocyte OT - subunit vaccine OT - tuberculosis OT - vaccine delivery EDAT- 2019/01/30 06:00 MHDA- 2019/04/27 06:00 CRDT- 2019/01/30 06:00 PHST- 2019/01/30 06:00 [pubmed] PHST- 2019/04/27 06:00 [medline] PHST- 2019/01/30 06:00 [entrez] AID - 10.4014/jmb.1809.09049 [pii] AID - 10.4014/jmb.1809.09049 [doi] PST - ppublish SO - J Microbiol Biotechnol. 2019 Mar 28;29(3):489-499. doi: 10.4014/jmb.1809.09049.