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-Gu & eacute;rin (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-c, IL-2, and/or TNF-a. 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 , 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. (c) 2025 The Author(s). Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).