Cell wall skeleton of Mycobacterium bovis BCG enhances the vaccine potential of antigen 85B against tuberculosis by inducing Th1 and Th17 responses

PLoS One. 2019 Mar 8;14(3):e0213536. doi: 10.1371/journal.pone.0213536. eCollection 2019.

Abstract

A safe and effective adjuvant is necessary to induce reliable protective efficacy of the protein-based vaccines against tuberculosis (TB). Mycobacterial components, such as synthetic cord factor and arabinogalactan, have been used as one of the adjuvant components. Mycobacterium bovis bacillus Calmette- Guérin cell-wall skeleton (BCG-CWS) has been used as an effective immune-stimulator. However, it is not proven whether BCG-CWS can be an effective adjuvant for the subunit protein vaccine of TB. In this study, we demonstrated that the BCG-CWS effectively coupled with Ag85B and enhanced the conjugated Ag85B activity on the maturation of dendritic cells (DCs). Ag85B-BCG-CWS-matured DCs induced significant Th1 and Th17 responses when compared to BCG-CWS or Ag85B alone. In addition, significant Ag85B-specific Th1 and Th17 responses were induced in Ag85B-BCG-CWS-immunized mice before infection with M. tuberculosis and maintained after infection. Moreover, Ag85B-BCG-CWS showed significant protective effect comparable to live BCG at 6 weeks after infection and maintained its protective efficacy at 32 weeks post-challenge, whereas live BCG did not. These results suggest that the BCG-CWS may be an effective adjuvant candidate for a protein-based vaccine against TB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antigens, Bacterial / immunology*
  • Antigens, Bacterial / pharmacology
  • Cell Wall / immunology*
  • Female
  • Mice
  • Mycobacterium bovis / immunology*
  • Mycobacterium tuberculosis / immunology*
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*
  • Th2 Cells / pathology
  • Tuberculosis / immunology*
  • Tuberculosis / pathology
  • Tuberculosis / prevention & control
  • Tuberculosis Vaccines / immunology*
  • Tuberculosis Vaccines / pharmacology

Substances

  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • Tuberculosis Vaccines

Grants and funding

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (2016R1E1A1A02921580), and was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHDI), funded by the Ministry of Health & Welfare, Republic Korea (HI17C0175).