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Clinical and Vaccine Immunology, October 2009, p. 1467-1475, Vol. 16, No. 10
1071-412X/09/$08.00+0     doi:10.1128/CVI.00237-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Multicistronic DNA Vaccine Induces Significant Protection against Tuberculosis in Mice and Offers Flexibility in the Expressed Antigen Repertoire{triangledown}

Fayaz-Ahmad Mir, Stefan H. E. Kaufmann,* and Ali Nasser Eddine

Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, Berlin 10117, Germany

Received 16 June 2009/ Returned for modification 21 July 2009/ Accepted 28 July 2009

Concerns about the safety and efficacy of Mycobacterium bovis bacillus Calmette-Guérin (BCG) emphasize the need for alternative tuberculosis (TB) vaccines. DNA vaccines are interesting candidates but are limited by the restricted antigen repertoire that they express. Traditional polycistronic vectors are large and have imbalanced expression. Recent advances in molecular genetics and cellular immunology have paved the way toward the rational design of an efficacious vaccine. We exploited self-cleaving peptide 2A from the foot-and-mouth disease virus, because of its small size and high cleavage activity, to generate an efficient TB DNA vaccine (V-2A). V-2A expresses three mycobacterial antigens, Rv3407, Ag85A, and HspX, in a single open reading frame joined by the 2A sequences, which lead to the segmentation of the long translated polypeptide into individual proteins by posttranslational modification. Our in vitro measurements revealed no differences at the transcriptional or translational level between V-2A and the monocistronic expression of the individual antigens. Mice vaccinated with V-2A developed antigen-specific cellular and humoral responses against all three antigens, imparting protection against Mycobacterium tuberculosis aerosol challenge equivalent to that imparted by BCG. These results have important implications for the rational design and development of efficacious recombinant subunit vaccines.

* Corresponding author. Mailing address: Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, Berlin 10117, Germany. Phone: 49-30-28460500. Fax: 49-30-28460501. E-mail: kaufmann{at}mpiib-berlin.mpg.de

{triangledown} Published ahead of print on 5 August 2009.

Clinical and Vaccine Immunology, October 2009, p. 1467-1475, Vol. 16, No. 10
1071-412X/09/$08.00+0     doi:10.1128/CVI.00237-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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