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Updated: May 24, 2026
Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice
Published on: September 19, 2016
Targeted delivery of the BCG vaccine to dendritic cells improves protective efficacy against Mycobacterium
Claudio Counoupas1, Annuurun Nisa2, Lucy Baker2
1Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia; Centre for Infection and Immunity, Centenary Institute, The University of Sydney, Camperdown, NSW 2006, Australia; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkin Centre, The University of Sydney, Camperdown, NSW 2006, Australia.
Abstract:
Tuberculosis (TB) is the world's deadliest infectious disease, and the current vaccine, Bacillus Calmette-Guérin (BCG), is only partially effective. We hypothesised that BCG interacts sub-optimally with dendritic cells (DCs), key mediators of adaptive immunity. To improve BCG's efficacy, we engineered the vaccine to express a single-chain variable fragment (scFv) targeting the DEC-205 receptor on DCs (BCG:DEC). This modification enhanced BCG interaction with DEC-205-expressing cells, resulting in increased uptake into host cells and cytokine/chemokine secretion. After vaccination of mice, BCG:DEC increased MHC-II expression on vaccine-site myeloid cells, showed enhanced uptake by skin-resident DC subsets and generated higher frequencies of multifunctional, cytokine-secreting CD4+ T cell populations. Compared to BCG alone, BCG:DEC provided improved and sustained protection up to 20 weeks post-challenge against Mycobacterium tuberculosis in mice. Thus, DC-targeted BCG is a promising approach for TB control.
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