A clinically approved oral vaccine against pneumotropic bacteria induces the terminal maturation of CD83 + immunostimulatory dendritic cells

Abstract

Dendritic cells (DCs) are important antigen-presenting cells of the immune system that have attracted interest as cellular adjuvants to induce immunity in clinical settings. We have investigated the effects of Broncho-Vaxom®, an oral vaccine composed of lysates from eight pneumotropic bacteria, on human monocyte-derived dendritic cells (moDCs). Broncho-Vaxom® induced the terminal maturation of CD83 + moDCs. MoDCs stimulated with Broncho-Vaxom® displayed a phenotype of activated DCs with high levels of major histocompatibility complex (MHC) molecules and increased levels of adhesion and co-stimulatory molecules. In addition, moDCs activated with Broncho-Vaxom® exhibited enhanced T cell-stimulatory capacity in the allogeneic mixed leukocyte reaction. Broncho-Vaxom® at 100 μg/ml was as potent as TNF-α at 1000 U/ml in activating human moDCs. Neither LPS-like activity nor bacterial DNA was found to be responsible for the maturation-inducing activity of Broncho-Vaxom®, suggesting that Broncho-Vaxom® contains other bacterial factors that are capable of inducing the terminal maturation of moDCs. In DC-based immunotherapy, Broncho-Vaxom® could be used as a stimulus of DC maturation, which meets the standards of good manufacturing practice (GMP). In addition, vaccination with Broncho-Vaxom®-loaded moDCs may be an attractive treatment option in preventing recurrent airway infection in predisposed individuals.