Enhanced tuberculosis control via leveraging dendritic cell-mediated Th1 responses in preventive and immunotherapeutic vaccine strategies

Abstract

Introduction: Insufficient vaccine efficacy of the Bacillus Calmette-Guérin (BCG) and long, expensive tuberculosis (TB) treatments highlight the need for better TB control measures. Methods: This study evaluated whether the adoptive transfer of dendritic cell (DC)-based vaccines pulsed with culture filtrate antigens (CFA) of Mycobacterium tuberculosis (Mtb) could enhance BCG efficacy and support anti-TB drug therapy. Results: In BCG-vaccinated mice, adoptive transfer of CFA-pulsed DCs promoted swift T cell recruitment to the lung parenchyma, reducing bacterial load within 1 week post-infection, promoting the generation of tissue-resident T cells and expansion of CD4+ T cells co-producing IFN-γ, IL-2, and/or TNF-α. The vaccine efficacy persisted for a prolonged period post-infection, with protection found in both high dose and low dose Mtb infection models. Additionally, CFA-DC administration during chemotherapy enhanced treatment efficacy, maintaining CD4+ T cell responses. In latent TB models, mice were protected from Mtb reactivation in both drug-sensitive and multidrug-resistant TB models. Conclusions: DC-based prophylactic and immunotherapeutic vaccine strategies enhance protective immunity during BCG vaccination and chemotherapy, offering new insights into TB control strategies.