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Infect Immun, April 1998, p. 1527-1533, Vol. 66, No. 4
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Vaccination with Plasmid DNA Encoding Mycobacterial Antigen 85A Stimulates a CD4+ and CD8+ T-Cell Epitopic Repertoire Broader than That Stimulated by Mycobacterium tuberculosis H37Rv Infection

Olivier Denis,1 Audrey Tanghe,1 Kamiel Palfliet,1 Fabienne Jurion,1 Thierry-P. van den Berg,2 Albert Vanonckelen,1 Josette Ooms,1 Eric Saman,3 Jeffrey B. Ulmer,4 Jean Content,1 and Kris Huygen1,*

Department of Virology, Pasteur Institute of Brussels,1 and Veterinary and Agrochemical Research Center (VAR),2 1180 Brussels, and Innogenetics Ghent, 9052 Ghent,3 Belgium, and Merck Research Laboratories, West Point, Pennsylvania 194864

Received 15 September 1997/Returned for modification 22 October 1997/Accepted 20 January 1998

Vaccination of mice with plasmid DNA carrying the gene for the major secreted mycobacterial antigen 85A (Ag85A) from Mycobacterium tuberculosis is a powerful technique for generating robust specific Th1 helper T-cell responses, CD8+-mediated cytotoxicity, and protection against M. tuberculosis challenge (K. Huygen et al., Nat. Med. 2:893-898, 1996). We have now analyzed in more detail the antigen-specific immune CD4+- and CD8+-T-cell responses induced in BALB/c mice vaccinated with Ag85A DNA and have compared these responses to those generated by intravenous infection with M. tuberculosis. T-cell-epitope mapping, as measured by interleukin-2 and gamma interferon secretion from splenic T cells restimulated in vitro with synthetic 20-mer peptides spanning the complete mature sequence of Ag85A, demonstrated that DNA vaccination stimulated a stronger and broader T-cell response than did M. tuberculosis infection. Moreover, elevated cytotoxic T lymphocyte (CTL) activity against Ag85A-transfected and peptide-pulsed P815 target cells could be generated exclusively by vaccination with plasmid DNA, not following M. tuberculosis infection. By using DNA vaccination, three Ag85A CTL epitopes with predicted major histocompatibility complex class I binding motifs were defined. One of them was previously reported as a dominant, promiscuously recognized T-cell epitope in healthy humans with primary infections. These data strengthen the potential of DNA vaccination with respect to inducing antituberculous immunity in humans.

* Corresponding author. Mailing address: Pasteur Institute of Brussels, Department Virology, 642 Engelandstraat, 1180 Brussels, Belgium. Phone: 32.2.373.33.70. Fax: 32.2.373.31.74. E-mail: chuygen{at}ben.vub.ac.be.




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Copyright © 1998 by the American Society for Microbiology. All rights reserved.