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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,{dagger} Leander Grode,2,{dagger} Jens Mattow,1 Maik Stein,1 Peggy Mann,1 Bernhard Knapp,3 Jeffrey Ulmer,4 and Stefan H. E. Kaufmann1*

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.

* Corresponding author. Mailing address: Dept. of Immunology, MPI for Infection Biology, Schumannstr. 21/22, D-10117 Berlin, Germany. Phone: 49 30 28460500. Fax: 49 30 28460501. E-mail: Kaufmann{at}mpiib-berlin.mpg.de.

Editor: D. L. Burns

{dagger} Both authors contributed equally.

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.



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