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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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