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Infection and Immunity, November 2004, p. 6471-6479, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6471-6479.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Application of Mycobacterial Proteomics to Vaccine Design: Improved Protection by Mycobacterium bovis BCG Prime-Rv3407 DNA Boost Vaccination against Tuberculosis

Hans Joachim Mollenkopf,^1, Leander Grode,^2, Jens Mattow,¹ Maik Stein,¹ Peggy Mann,¹ Bernhard Knapp,³ Jeffrey Ulmer,⁴ and Stefan H. E. Kaufmann^1*

Department of Immunology, Max Planck Institute for Infection Biology, Berlin,¹ Vakzine Projekt-Management GmbH, Braunschweig,² Preclinical Research Vaccines, Chiron Behring GmbH & Co., Marburg, Germany,³ Chiron Corp., Emeryville, California⁴

Received 16 May 2004/ Returned for modification 28 June 2004/ Accepted 5 August 2004

Information from comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guérin (BCG) principally allows prediction of potential vaccine candidates. Thirty-six M. tuberculosis DNA vaccine candidates identified by comparative proteome analysis were evaluated in the mouse model for protection against low-dose aerosol M. tuberculosis infection. We identified the DNA vaccine candidate Rv3407 as a protective antigen and analyzed putative major histocompatibility complex class I epitopes by computational predictions and gamma interferon Elispot assays. Importantly, we discovered that the DNA vaccine Rv3407 improved the efficacy of BCG vaccination in a heterologous prime-boost vaccination protocol. Our data demonstrate the rationale of a combination of proteomics, epitope prediction, and broad screening of putative antigens for identification of novel DNA vaccine candidates. Furthermore, our experiments show that heterologous prime-boost vaccination with a defined antigen boost "on top" of a BCG primer provides superior protection against tuberculosis over vaccination with BCG alone.

Editor: D. L. Burns

Both authors contributed equally.

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