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  • 제23권2호
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  • Pages.16.1-16.19
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  • 2023
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  • 1598-2629(pISSN)
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  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
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Protective Efficacy and Immunogenicity of Rv0351/Rv3628 Subunit Vaccine Formulated in Different Adjuvants Against Mycobacterium tuberculosis Infection

  • Kee Woong Kwon (Department of Microbiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Tae Gun Kang (Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University) ;
  • Ara Lee (Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University) ;
  • Seung Mo Jin (SKKU Advanced Institute of Nanotechnology (SAINT), Department of Nano Engineering, School of Chemical Engineering, Sungkyunkwan University (SKKU)) ;
  • Yong Taik Lim (SKKU Advanced Institute of Nanotechnology (SAINT), Department of Nano Engineering, School of Chemical Engineering, Sungkyunkwan University (SKKU)) ;
  • Sung Jae Shin (Department of Microbiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Sang-Jun Ha (Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University)
  • 투고 : 2022.07.12
  • 심사 : 2023.01.17
  • 발행 : 2023.04.30
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초록

Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for tuberculosis (TB) prevention. Previously, our group demonstrated the vaccine potential of Rv0351 and Rv3628 against Mycobacterium tuberculosis (Mtb) infection by directing Th1-biased CD4+ T cells co-expressing IFN-γ, TNF-α, and IL-2 in the lungs. Here, we assessed immunogenicity and vaccine potential of the combined Ags (Rv0351/Rv3628) formulated in different adjuvants as subunit booster in BCG-primed mice against hypervirulent clinical Mtb strain K (Mtb K). Compared to BCG-only or subunit-only vaccine, BCG prime and subunit boost regimen exhibited significantly enhanced Th1 response. Next, we evaluated the immunogenicity to the combined Ags when formulated with four different types of monophosphoryl lipid A (MPL)-based adjuvants: 1) dimethyldioctadecylammonium bromide (DDA), MPL, and trehalose dicorynomycolate (TDM) in liposome form (DMT), 2) MPL and Poly I:C in liposome form (MP), 3) MPL, Poly I:C, and QS21 in liposome form (MPQ), and 4) MPL and Poly I:C in squalene emulsion form (MPS). MPQ and MPS displayed greater adjuvancity in Th1 induction than DMT or MP did. Especially, BCG prime and subunit-MPS boost regimen significantly reduced the bacterial loads and pulmonary inflammation against Mtb K infection when compared to BCG-only vaccine at a chronic stage of TB disease. Collectively, our findings highlighted the importance of adjuvant components and formulation to induce the enhanced protection with an optimal Th1 response.

키워드

과제정보

This work was supported by the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (HV20C0144, HV20C0139, and HV22C0079). This study was also supported in part by the Yonsei University Research Fund (Post Doc. Researcher Supporting Program) of 2021 (project no.: 2021-12-0156 to T.G.K). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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