Article abstract
Nature Medicine 15, 267 - 276 (2009)
Published online: 1 March 2009 | doi:10.1038/nm.1928
Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells
Chinnaswamy Jagannath1, Devin R Lindsey1, Subramanian Dhandayuthapani2, Yi Xu3, Robert L Hunter Jr1 & N Tony Eissa3
Abstract
The variable efficacy of Bacille Calmette Guerin (BCG) vaccination against tuberculosis has prompted efforts to improve the vaccine. In this study, we used autophagy to enhance vaccine efficacy against tuberculosis in a mouse model. We examined the effect of autophagy on the processing of the immunodominant mycobacterial antigen Ag85B by antigen presenting cells (APCs), macrophages and dendritic cells (DCs). We found that rapamycin-induced autophagy enhanced Ag85B presentation by APCs infected with wild-type Mycobacterium tuberculosis H37Rv, H37Rv-derived 
fbpA attenuated candidate vaccine or BCG. Furthermore, rapamycin enhanced localization of mycobacteria with autophagosomes and lysosomes. Rapamycin-enhanced antigen presentation was attenuated when autophagy was suppressed by 3-methyladenine or by small interfering RNA against beclin-1. Notably, mice immunized with rapamycin-treated DCs infected with either fbpA or BCG showed enhanced T helper type 1–mediated protection when challenged with virulent Mycobacterium tuberculosis. Finally, overexpression of Ag85B in BCG induced autophagy in APCs and enhanced immunogenicity in mice, suggesting that vaccine efficacy can be enhanced by augmenting autophagy-mediated antigen presentation.
- Department of Pathology and Laboratory Medicine, University of Texas Health Sciences Center (UTHSC), 6431, Fannin, Houston, Texas 77030, USA.
- Regional Academic Health Center and Department of Microbiology and Immunology, UTHSC-San Antonio, Edinburg, Texas 78541, USA.
- Department of Medicine, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA.
Correspondence to: Chinnaswamy Jagannath1 e-mail: Chinnaswamy.Jagannath@uth.tmc.edu
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