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Infection and Immunity, September 2001, p. 5403-5411, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5403-5411.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Protective Efficacy of a DNA Vaccine Encoding Antigen 85A from Mycobacterium bovis BCG against Buruli Ulcer

Audrey Tanghe,1 Jean Content,2 Jean-Paul Van Vooren,3 Françoise Portaels,4 and Kris Huygen1,*

Mycobacterial Immunology1 and Molecular Microbiology,2 Pasteur Institute of Brussels, and Hôpital Erasme ULB,3 Brussels, and Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp,4 Belgium

Received 26 February 2001/Returned for modification 9 April 2001/Accepted 6 June 2001

Buruli ulcer, caused by Mycobacterium ulcerans, is characterized by deep and necrotizing skin lesions, mostly on the arms and legs. Together with tuberculosis and leprosy, this mycobacterial disease has become a major health problem in tropical and subtropical regions, particularly in central and western Africa. No specific vaccine is available for Buruli ulcer. There is, however, evidence in the literature that suggests a cross-reactive protective role of the tuberculosis vaccine M. bovis BCG. To identify potential mechanisms for this cross-protection, we identified and characterized the M. ulcerans homologue of the important protective mycobacterial antigen 85 (Ag85A) from BCG. The homologue is well conserved in M. ulcerans, showing 84.1% amino acid sequence identity and 91% conserved residues compared to the sequence from BCG. This antigen was sufficiently conserved to allow cross-reactive protection, as demonstrated by the ability of M. ulcerans- infected mice to exhibit strong cellular immune responses to both BCG and its purified Ag85 complex. To further address the mechanism of cross-reactive protection, we demonstrate here that prior vaccination with either BCG or plasmid DNA encoding BCG Ag85A is capable of significantly reducing the bacterial load in the footpads of M. ulcerans- infected mice, as determined by Ziehl-Neelsen staining and by actual counting of CFU on 7H11 Middlebrook agar. Together, the results reported here support the potential of a cross-protective Ag85-based future vaccine against tuberculosis, Buruli ulcer, and leprosy.

* Corresponding author. Mailing address: Mycobacterial Immunology, Pasteur Institute of Brussels, 642 Engelandstraat, B-1180 Brussels, Belgium. Phone: 32.2.373.33.70. Fax: 32.2.373.33.67. E-mail: khuygen{at}pasteur.be.

Infection and Immunity, September 2001, p. 5403-5411, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5403-5411.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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