A Dendritic Cell-Activating Rv1876 Protein Elicits Mycobacterium Bovis BCG-Prime Effect via Th1-Immune Response

Biomolecules. 2021 Sep 3;11(9):1306. doi: 10.3390/biom11091306.

Abstract

The widely administered tuberculosis (TB) vaccine, Bacillus Calmette-Guerin (BCG), is the only licensed vaccine, but has highly variable efficiency against childhood and pulmonary TB. Therefore, the BCG prime-boost strategy is a rational solution for the development of new TB vaccines. Studies have shown that Mycobacterium tuberculosis (Mtb) culture filtrates contain proteins that have promising vaccine potential. In this study, Rv1876 bacterioferritin was identified from the culture filtrate fraction with strong immunoreactivity. Its immunobiological potential has not been reported previously. We found that recombinant Rv1876 protein induced dendritic cells' (DCs) maturation by MAPK and NF-κB signaling activation, induced a T helper type 1 cell-immune response, and expanded the population of the effector/memory T cell. Boosting BCG with Rv1876 protein enhanced the BCG-primed Th1 immune response and reduced the bacterial load in the lung compared to those of BCG alone. Thus, Rv1876 is a good target for the prime-boost strategy.

Keywords: BCG-prime boost; Rv1876; Th1 polarization; dendritic cell; mycobacterium tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Cell Proliferation
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Female
  • Immunity*
  • Immunologic Memory
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mutation / genetics
  • Mycobacterium bovis / growth & development
  • Mycobacterium bovis / immunology*
  • Th1 Cells / immunology*
  • Vaccination

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Cytokines