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Infection and Immunity, May 2003, p. 2933-2937, Vol. 71, No. 5
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.5.2933-2937.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Immune Response Induced by Recombinant Mycobacterium bovis BCG Producing the Cholera Toxin B Subunit

Franck Biet,1,{dagger} Laurent Kremer,1 Isabelle Wolowczuk,2 Myriam Delacre,2 and Camille Locht1*

Laboratoire de Microbiologie Génétique et Moléculaire, INSERM U447,1 CNRS UMR 8527, IBL, Institut Pasteur de Lille, F-59019 Lille, France2

Received 12 August 2002/ Returned for modification 25 October 2002/ Accepted 18 February 2003

The pentameric form of the cholera toxin B subunit (CTB) is known to be a strong mucosal adjuvant and stimulates antigen-specific secretory immunoglobulin A (IgA) and systemic antibody responses to antigens when given by mucosal routes. To deliver CTB for prolonged periods of time to the respiratory mucosa, we constructed a Mycobacterium bovis bacillus Calmette-Guérin (BCG) strain that produces and secretes assembled pentameric CTB. Mice immunized intranasally (i.n.) with recombinant BCG (rBCG) developed a stronger anti-BCG IgA response in bronchoalveolar lavage fluids (BALF) than mice immunized with nonrecombinant BCG. The total IgA response in the BALF of mice immunized with rBCG was also stronger than that in BALF of mice immunized with the nonrecombinant strain. The induction of IgA was well correlated with an increased production of transforming growth factor ß1. Simultaneous administration of intraperitoneally delivered ovalbumin and of i.n. delivered CTB-producing BCG induced a long-lasting ovalbumin-specific mucosal IgA response as well as a systemic IgG response, both of which were significantly higher than those in mice immunized with nonrecombinant BCG together with ovalbumin. These results suggest that the CTB-producing BCG may be a powerful adjuvant to be considered for future mucosal vaccine development.


* Corresponding author. Mailing address: Laboratoire de Microbiologie Génétique et Moléculaire, INSERM U447, Institut Pasteur de Lille, 1 rue du Prof. Calmette, F-59019 Lille Cedex, France. Phone: (33) 3.20.87.11.51. Fax: (33) 3.20.87.11.58. E-mail: camille.locht{at}pasteur-lille.fr.

{dagger} Present address: UR 918 Pathologie Infectieuse et Immunologie, INRA Centre de Tours, 37380 Nouzilly, France.

Editor: S. H. E. Kaufmann


Infection and Immunity, May 2003, p. 2933-2937, Vol. 71, No. 5
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.5.2933-2937.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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